Continued from EC 1.14.99
EC 1.15 Acting on superoxide as acceptor
EC 1.16 Oxidizing metal ions
EC 1.16.1 With NAD+ or NADP+ as acceptor
EC 1.16.3 With oxygen as acceptor
EC 1.16.5 With quinone or similar compound as acceptor
EC 1.16.8 With flavin as acceptor
EC 1.16.98 With other, known, physiological acceptor
EC 1.17 Acting on CH or CH2 groups
EC 1.17.1 With NAD+ or NADP+ as acceptor
EC 1.17.3 With oxygen as acceptor
EC 1.17.4 With disulfide as acceptor
EC 1.17.5 With a quinone or similar compound as acceptor
EC 1.17.7 With an iron-sulfur protein as acceptor
EC 1.17.98 With other, known, physiological acceptors
EC 1.17.99 With unknown physiological acceptors
EC 1.18 Acting on iron-sulfur proteins as donors
EC 1.18.1 With NAD+ or NADP+ as acceptor
EC 1.18.3 With H+ as acceptor
EC 1.18.6 With dinitrogen as acceptor
EC 1.18.96 With other, known, physiological acceptors
EC 1.18.99 With H+ as acceptor
EC 1.19 Acting on reduced flavodoxin as donor
EC 1.19.1 With NAD+ or NADP+ as acceptor
EC 1.19.6 With dinitrogen as acceptor
EC 1.20 Acting on phosphorus or arsenic in donors
EC 1.20.1 With NAD(P)+ as acceptor
EC 1.20.4 With disulfide as acceptor
EC 1.20.98 With other, known, physiological acceptors
EC 1.20.99 With other acceptors
EC 1.21 Acting on X-H and Y-H to form an X-Y bond
EC 1.21.3 With oxygen as acceptor
EC 1.21.4 With a disulfide as acceptor
EC 1.21.99 With unknown physiological acceptors
EC 1.22 Acting on halogen in donors
EC 1.22.1 With NAD(P)+ as acceptor
EC 1.23 Reducing C-O-C group as acceptor
EC 1.23.1 With NAD(P)+ as acceptor
EC 1.23.5 With a quinone or related compound as acceptor
EC 1.97 Other oxidoreductases
Accepted name: superoxide dismutase
Reaction: 2 superoxide + 2 H+ = O2 + H2O2
Glossary: superoxide = O2•–
Other name(s): superoxidase dismutase; copper-zinc superoxide dismutase; Cu-Zn superoxide dismutase; ferrisuperoxide dismutase; superoxide dismutase I; superoxide dismutase II; SOD; Cu,Zn-SOD; Mn-SOD; Fe-SOD; SODF; SODS; SOD-1; SOD-2; SOD-3; SOD-4; hemocuprein; erythrocuprein; cytocuprein; cuprein ; hepatocuprein
Systematic name: superoxide:superoxide oxidoreductase
Comments: A metalloprotein; also known as erythrocuprein, hemocuprein or cytocuprein. Enzymes from most eukaryotes contain both copper and zinc; those from mitochondria and most prokaryotes contain manganese or iron.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9054-89-1
References:
1. Keele, B.B., McCord, J.M. and Fridovich, I. Further characterization of bovine superoxide dismutase and its isolation from bovine heart. J. Biol. Chem. 246 (1971) 2875-2880. [PMID: 4324341]
2. Sawada, Y., Ohyama, T. and Yamazaki, I. Preparation and physicochemical properties of green pea superoxide dismutase. Biochim. Biophys. Acta 268 (1972) 305-312. [PMID: 4337330]
3. Vance, P.G., Keele, B.B. and Rajagopalan, K.V. Superoxide dismutase from Streptococcus mutans. Isolation and characterization of two forms of the enzyme. J. Biol. Chem. 247 (1972) 4782-4786. [PMID: 4559499]
Accepted name: superoxide reductase
Reaction: superoxide + reduced rubredoxin + 2 H+ = H2O2 + oxidized rubredoxin
Glossary entries:
rubredoxin = iron-containing protein found in sulfur-metabolizing bacteria and archaea, participating in electron transfer
Other names: neelaredoxin; desulfoferrodoxin
Systematic name: rubredoxin:superoxide oxidoreductase
Comments: The enzyme contains non-heme iron.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 250679-67-5
References:
1. Jenney, F.E., Jr., Verhagen, M.F.J.M., Cui, X. and Adams, M.W.W. Anaerobic microbes: Oxygen detoxification without superoxide dismutase. Science 286 (1999) 306-309. [PMID: 10514376]
2. Yeh, A.P., Hu, Y., Jenney, F.E., Jr., Adams, M.W.W. and Rees, D.C. Structures of the superoxide reductase from Pyrococcus furiosus in the oxidized and reduced states. Biochemistry 39 (2000) 2499-2508. [PMID: 10704199]
3. Lombard, M., Fontecave, M., Touati, D. and Niviere, V. Reaction of the desulfoferrodoxin from Desulfoarculus baarsii with superoxide anion. Evidence for a superoxide reductase activity. J. Biol. Chem. 275 (2000) 115-121. [PMID: 10617593]
4. Abreu, I.A., Saraiva, L.M., Carita, J., Huber, H., Stetter, K.O., Cabelli, D. and Teixeira, M. Oxygen detoxification in the strict anaerobic archaeon Archaeoglobus fulgidus: superoxide scavenging by neelaredoxin. Mol. Microbiol. 38 (2000) 322-334. [PMID: 11069658]
EC 1.16.1 With NAD+ or NADP+ as acceptor
EC 1.16.3 With oxygen as acceptor
EC 1.16.98 With other, known, physiological acceptor
Accepted name: mercury(II) reductase
Reaction: Hg + NADP+ + H+ = Hg2+ + NADPH
Other name(s): mercuric reductase; mercurate(II) reductase; mercuric ion reductase; mercury reductase; reduced NADP:mercuric ion oxidoreductase; mer A
Systematic name: Hg:NADP+ oxidoreductase
Comments: A dithiol enzyme.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 67880-93-7
References:
1. Fox, B.S. and Walsh, C.T. Mercuric reductase. Purification and characterization of a transposon-encoded flavoprotein containing an oxidation-reduction-active disulfide. J. Biol. Chem. 257 (1982) 2498-2503. [PMID: 6277900]
2. Fox, B.S. and Walsh, C.T. Mercuric reductase - homology to glutathione-reductase and lipoamide dehydrogenase - iodoacetamide alkylation and sequence of the active-site peptide. Biochemistry 22 (1983) 4082-4088.
Accepted name: diferric-transferrin reductase
Reaction: transferrin[Fe(II)]2 + NAD+ + H+ = transferrin[Fe(III)]2 + NADH
Other name(s): diferric transferrin reductase; NADH diferric transferrin reductase; transferrin reductase
Systematic name: transferrin[Fe(II)]2:NAD+ oxidoreductase
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 105238-49-1
References:
1. Löw, H., Sun, I.L., Navas, P., Grebing, C., Crane, F.L. and Morré, D.J. Transplasmalemma electron transport from cells is part of a diferric transferrin reductase system. Biochem. Biophys. Res. Commun. 139 (1986) 1117-1123. [PMID: 3767994]
[EC 1.16.1.3 Deleted entry: aquacobalamin reductase. This entry has been deleted since no specific enzyme catalysing this activity has been identified and it has been shown that aquacobalamin is efficiently reduced by free dihydroflavins and by non-specific reduced flavoproteins. (EC 1.16.1.3 created 1972 as EC 1.6.99.8, transferred 2002 to EC 1.16.1.3, modified 2020, deleted 2020)]
[EC 1.16.1.4 Deleted entry: cob(II)alamin reductase. This entry has been deleted since no specific enzyme catalysing this activity has been identified and it has been shown that cob(II)alamin is efficiently reduced by free dihydroflavins and by non-specific reduced flavoproteins (EC 1.16.1.4 created 1972 as EC 1.6.99.9, transferred 2002 to EC 1.16.1.4, deleted 2021)]
[EC 1.16.1.5 Deleted entry: aquacobalamin reductase (NADPH). This entry has been deleted since the enzyme the entry was based on was later shown to be EC 1.2.1.51, pyruvate dehydrogenase (NADP+). On the other hand, it has been shown that non-enzymatic reduction of cob(III)alamin to cob(II)alamin occurs efficiently in the presence of free dihydroflavins or non-specific reduced flavoproteins. (EC 1.16.1.5 created 1989 as EC 1.6.99.11, transferred 2002 to EC 1.16.1.5, modified 2020, deleted 2020)]
Accepted name: cyanocobalamin reductase
Reaction: 2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP+ = 2 cyanocob(III)alamin + 2 [cyanocobalamin reductase] + NADPH + H+
Other name(s): MMACHC (gene name); CblC; cyanocobalamin reductase (NADPH, cyanide-eliminating); cyanocobalamin reductase (NADPH, CN-eliminating); NADPH:cyanocob(III)alamin oxidoreductase (cyanide-eliminating); cob(I)alamin, cyanide:NADP+ oxidoreductase; cyanocobalamin reductase (cyanide-eliminating)
Systematic name: cob(II)alamin, hydrogen cyanide:NADP+ oxidoreductase
Comments: The mammalian enzyme, which is cytosolic, can bind internalized cyanocobalamin and process it to cob(II)alamin by removing the upper axial ligand. The product remains bound to the protein, which, together with its interacting partner MMADHC, transfers it directly to downstream enzymes involved in adenosylcobalamin and methylcobalamin biosynthesis. In addition to its decyanase function, the mammalian enzyme also catalyses an entirely different chemical reaction with alkylcobalamins, using the thiolate of glutathione for nucleophilic displacement, generating cob(I)alamin and the corresponding glutathione thioether (cf. EC 2.5.1.151, alkylcobalamin dealkylase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 131145-00-1
References:
1. Watanabe, F., Oki, Y., Nakano, Y. and Kitaoka, S. Occurrence and characterization of cyanocobalamin reductase (NADPH; CN-eliminating) involved in decyanation of cyanocobalamin in Euglena gracilis. J. Nutr. Sci. Vitaminol. 34 (1988) 1-10. [PMID: 3134526]
2. Kim, J., Gherasim, C. and Banerjee, R. Decyanation of vitamin B12 by a trafficking chaperone. Proc. Natl. Acad. Sci. USA 105 (2008) 14551-14554. [PMID: 18779575]
3. Koutmos, M., Gherasim, C., Smith, J.L. and Banerjee, R. Structural basis of multifunctionality in a vitamin B12-processing enzyme. J. Biol. Chem. 286 (2011) 29780-29787. [PMID: 21697092]
4. Mah, W., Deme, J.C., Watkins, D., Fung, S., Janer, A., Shoubridge, E.A., Rosenblatt, D.S. and Coulton, J.W. Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B12 metabolism. Mol Genet Metab 108 (2013) 112-118. [PMID: 23270877]
Accepted name: ferric-chelate reductase (NADH)
Reaction: 2 Fe(II)-siderophore + NAD+ + H+ = 2 Fe(III)-siderophore + NADH
Other name(s): ferric chelate reductase (ambiguous); iron chelate reductase (ambiguous); NADH:Fe3+-EDTA reductase; NADH2:Fe3+ oxidoreductase; ferB (gene name); Fe(II):NAD+ oxidoreductase
Systematic name: Fe(II)-siderophore:NAD+ oxidoreductase
Comments: Contains FAD. The enzyme catalyses the reduction of bound ferric iron in a variety of iron chelators (siderophores), resulting in the release of ferrous iron. The plant enzyme is Involved in the transport of iron across plant plasma membranes. The enzyme from the bacterium Paracoccus denitrificans can also reduce chromate. cf. EC 1.16.1.9, ferric-chelate reductase (NADPH) and EC 1.16.1.10, ferric-chelate reductase [NAD(P)H].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 120720-17-4
References:
1. Askerlund, P., Larrson, C. and Widell, S. Localization of donor and acceptor sites of NADH dehydrogenase activities using inside-out and right-side-out plasma membrane vesicles from plants. FEBS Lett. 239 (1988) 23-28.
2. Brüggemann, W. and Moog, P.R. NADH-dependent Fe3+ EDTA and oxygen reduction by plasma membrane vesicles from barley roots. Physiol. Plant. 75 (1989) 245-254.
3. Brüggemann, W., Moog, P.R., Nakagawa, H., Janiesch, P. and Kuiper, P.J.C. Plasma membrane-bound NADH:Fe3+-EDTA reductase and iron deficiency in tomato (Lycopersicon esculentum). Is there a Turbo reductase ? Physiol. Plant. 79 (1990) 339-346.
4. Buckhout, T.J. and Hrubec, T.C. Pyridine nucleotide-dependent ferricyanide reduction associated with isolated plasma membranes of maize (Zea mays L.) roots. Protoplasma 135 (1986) 144-154.
5. Sandelius, A.S., Barr, R., Crane, F.L. and Morré, D.J. Redox reactions of plasma membranes isolated from soybean hypocotyls by phase partition. Plant Sci. 48 (1986) 1-10.
6. Mazoch, J., Tesarik, R., Sedlacek, V., Kucera, I. and Turanek, J. Isolation and biochemical characterization of two soluble iron(III) reductases from Paracoccus denitrificans. Eur. J. Biochem. 271 (2004) 553-562. [PMID: 14728682]
Accepted name: [methionine synthase] reductase
Reaction: 2 [methionine synthase]-methylcob(III)alamin + 2 S-adenosyl-L-homocysteine + NADP+ = 2 [methionine synthase]-cob(II)alamin + NADPH + H+ + 2 S-adenosyl-L-methionine
For diagram of reaction, click here
Other name(s): methionine synthase cob(II)alamin reductase (methylating); methionine synthase reductase; [methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing); [methionine synthase]-methylcob(I)alamin,S-adenosylhomocysteine:NADP+ oxidoreductase
Systematic name: [methionine synthase]-methylcob(III)alamin,S-adenosyl-L-homocysteine:NADP+ oxidoreductase
Comments: In humans, the enzyme is a flavoprotein containing FAD and FMN. The substrate of the enzyme is the inactivated cobalt(II) form of EC 2.1.1.13, methionine synthase. Electrons are transferred from NADPH to FAD to FMN. Defects in this enzyme lead to hereditary hyperhomocysteinemia.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 207004-87-3
References:
1. Leclerc, D., Wilson, A., Dumas, R., Gafuik, C., Song, D., Watkins, D., Heng, H.H.Q., Rommens, J.M., Scherer, S.W., Rosenblatt, D.S., Gravel, R.A. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Proc. Natl. Acad. Sci. USA 95 (1998) 3059-3064. [PMID: 9501215]
2. Olteanu, H. and Banerjee, R. Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. J. Biol. Chem. 276 (2001) 35558-35563. [PMID: 11466310]
3. Olteanu, H., Munson, T. and Banerjee, R. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry 41 (2002) 13378-13385. [PMID: 12416982]
Accepted name: ferric-chelate reductase (NADPH)
Reaction: 2 Fe(II)-siderophore + NADP+ + H+ = 2 Fe(III)-siderophore + NADPH
Other name(s): ferric chelate reductase (ambiguous); iron chelate reductase (ambiguous); NADPH:Fe3+-EDTA reductase; NADPH-dependent ferric reductase; yqjH (gene name); Fe(II):NADP+ oxidoreductase
Systematic name: Fe(II)-siderophore:NADP+ oxidoreductase
Comments: Contains FAD. The enzyme, which is widespread among bacteria, catalyses the reduction of ferric iron bound to a variety of iron chelators (siderophores), including ferric triscatecholates and ferric dicitrate, resulting in the release of ferrous iron. The enzyme from the bacterium Escherichia coli has the highest efficiency with the hydrolysed ferric enterobactin complex ferric N-(2,3-dihydroxybenzoyl)-L-serine [3]. cf. EC 1.16.1.7, ferric-chelate reductase (NADH) and EC 1.16.1.10, ferric-chelate reductase [NAD(P)H].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 120720-17-4
References:
1. Bamford, V.A., Armour, M., Mitchell, S.A., Cartron, M., Andrews, S.C. and Watson, K.A. Preliminary X-ray diffraction analysis of YqjH from Escherichia coli: a putative cytoplasmic ferri-siderophore reductase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 (2008) 792-796. [PMID: 18765906]
2. Wang, S., Wu, Y. and Outten, F.W. Fur and the novel regulator YqjI control transcription of the ferric reductase gene yqjH in Escherichia coli. J. Bacteriol. 193 (2011) 563-574. [PMID: 21097627]
3. Miethke, M., Hou, J. and Marahiel, M.A. The Siderophore-Interacting Protein YqjH Acts as a Ferric Reductase in Different Iron Assimilation Pathways of Escherichia coli. Biochemistry (2011) . [PMID: 22098718]
Accepted name: ferric-chelate reductase [NAD(P)H]
Reaction: 2 Fe(II)-siderophore + NAD(P)+ + H+ = 2 Fe(III)-siderophore + NAD(P)H
Other name(s): ferric reductase (ambiguous)
Systematic name: Fe(II)-siderophore:NAD(P)+ oxidoreductase
Comments: A flavoprotein. The enzyme catalyses the reduction of bound ferric iron in a variety of iron chelators (siderophores), resulting in the release of ferrous iron. The enzyme from the hyperthermophilic archaeon Archaeoglobus fulgidus is not active with uncomplexed Fe(III). cf. EC 1.16.1.7, ferric-chelate reductase (NADH) and EC 1.16.1.9, ferric-chelate reductase (NADPH).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Vadas, A., Monbouquette, H.G., Johnson, E. and Schroder, I. Identification and characterization of a novel ferric reductase from the hyperthermophilic Archaeon Archaeoglobus fulgidus. J. Biol. Chem. 274 (1999) 36715-36721. [PMID: 10593977]
2. Chiu, H.J., Johnson, E., Schroder, I. and Rees, D.C. Crystal structures of a novel ferric reductase from the hyperthermophilic archaeon Archaeoglobus fulgidus and its complex with NADP+. Structure 9 (2001) 311-319. [PMID: 11525168]
Contents
EC 1.16.3.1 ferroxidase
EC 1.16.3.2 bacterial non-heme ferritin
EC 1.16.3.3 manganese oxidase
EC 1.16.3.4 cuproxidase
Accepted name: ferroxidase
Reaction: 4 Fe(II) + 4 H+ + O2 = 4 Fe(III) + 2 H2O
Other name(s): ceruloplasmin; caeruloplasmin; ferroxidase I; iron oxidase, iron(II):oxygen oxidoreductase; ferro:O2 oxidoreductase; iron II:oxygen oxidoreductase; hephaestin; HEPH
Systematic name: Fe(II):oxygen oxidoreductase
Comments: The enzyme in blood plasma (ceruloplasmin) belongs to the family of multicopper oxidases. In humans it accounts for 95% of plasma copper. It oxidizes Fe(II) to Fe(III), which allows the subsequent incorporation of the latter into proteins such as apotransferrin and lactoferrin. An enzyme from iron oxidizing bacterium strain TI-1 contains heme a.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9031-37-2, 104404-69-5
References:
1. Osaki, S. Kinetic studies of ferrous ion oxidation with crystalline human ferroxidase (ceruloplasmin). J. Biol. Chem. 241 (1966) 5053-5059. [PMID: 5925868]
2. Osaki, S. and Walaas, O. Kinetic studies of ferrous ion oxidation with crystalline human ferroxidase. II. Rate constants at various steps and formation of a possible enzyme-substrate complex. J. Biol. Chem. 242 (1967) 2653-2657. [PMID: 6027241]
3. Lindley, P.F. Card, G. Zaitseva, I. Zaitsev, V. Reinhammar, B. SelinLindgren, E. and Yoshida, K. An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity. J. Biol. Inorg. Chem. 2 (1997) 454-463.
4. Takai, M., Kamimura, K. and Sugio, T. A new iron oxidase from a moderately thermophilic iron oxidizing bacterium strain TI-1. Eur. J. Biochem. 268 (2001) 1653-1658. [PMID: 11248684]
5. Chen, H., Attieh, Z.K., Su, T., Syed, B.A., Gao, H., Alaeddine, R.M., Fox, T.C., Usta, J., Naylor, C.E., Evans, R.W., McKie, A.T., Anderson, G.J. and Vulpe, C.D. Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice. Blood 103 (2004) 3933-3939. [PMID: 14751926]
Accepted name: bacterial non-heme ferritin
Reaction: 4 Fe(II) + O2 + 6 H2O = 4 [FeO(OH)] + 8 H+ (overall reaction)
(1a) 2 Fe(II) + O2 + 4 H2O = 2 [FeO(OH)] + 4 H+ + H2O2
(1b) 2 Fe(II) + H2O2 + 2 H2O = 2 [FeO(OH)] + 4 H+
Glossary: [FeO(OH)] = iron(III) oxide-hydroxide
Other name(s): FtnA; HuHF
Systematic name: Fe(II):oxygen oxidoreductase ([FeO(OH)]core-producing)
Comments: Ferritins are intracellular iron-storage and detoxification proteins found in all kingdoms of life. They are formed from two subunits that co-assemble in various ratios to form a spherical protein shell. Thousands of mineralized iron atoms are stored within the core of the structure. The product of dioxygen reduction by the bacterial non-heme ferritin is hydrogen peroxide, which is consumed in a subsequent reaction.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Hudson, A.J., Andrews, S.C., Hawkins, C., Williams, J.M., Izuhara, M., Meldrum, F.C., Mann, S., Harrison, P.M. and Guest, J.R. Overproduction, purification and characterization of the Escherichia coli ferritin. Eur. J. Biochem. 218 (1993) 985-995. [PMID: 8281950]
2. Stillman, T.J., Hempstead, P.D., Artymiuk, P.J., Andrews, S.C., Hudson, A.J., Treffry, A., Guest, J.R. and Harrison, P.M. The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe3+ and Zn2+ derivatives. J. Mol. Biol. 307 (2001) 587-603. [PMID: 11254384]
3. Bou-Abdallah, F., Yang, H., Awomolo, A., Cooper, B., Woodhall, M.R., Andrews, S.C. and Chasteen, N.D. Functionality of the three-site ferroxidase center of Escherichia coli bacterial ferritin (EcFtnA). Biochemistry 53 (2014) 483-495. [PMID: 24380371]
Accepted name: manganese oxidase
Reaction: 4 Mn2+ + 2 O2 + 4 H2O = 4 MnIVO2 + 8 H+ (overall reaction)
(1a) 4 Mn2+ + O2 + 4 H+ = 4 Mn3+ + 2 H2O
(1b) 4 Mn3+ + O2 + 6 H2O = 4 MnIVO2 + 12 H+
Other name(s): mnxG (gene name); mofA (gene name); moxA (gene name); cotA (gene name)
Systematic name: manganese(II):oxygen oxidoreductase
Comments: The enzyme, which belongs to the multicopper oxidase family, is found in many bacterial strains. It oxidizes soluble manganese(II) to insoluble manganese(IV) oxides. Since the enzyme is localized to the outer surface of the cell, its activity usually results in encrustation of the cells by the oxides. The physiological function of bacterial manganese(II) oxidation remains unclear.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Corstjens, P.L.A.M., de Vrind, J.P.M., Goosen, T. and de Vrind-de Jong, E.W. Identification and molecular analysis of the Leptothrix discophora SS-1 mofA gene, a gene putatively encoding a manganese-oxidizing protein with copper domains. Geomicrobiol. J. 14 (1997) 91-108.
2. Francis, C.A., Casciotti, K.L. and Tebo, B.M. Localization of Mn(II)-oxidizing activity and the putative multicopper oxidase, MnxG, to the exosporium of the marine Bacillus sp. strain SG-1. Arch. Microbiol. 178 (2002) 450-456. [PMID: 12420165]
3. Ridge, J.P., Lin, M., Larsen, E.I., Fegan, M., McEwan, A.G. and Sly, L.I. A multicopper oxidase is essential for manganese oxidation and laccase-like activity in Pedomicrobium sp. ACM 3067. Environ Microbiol 9 (2007) 944-953. [PMID: 17359266]
4. Geszvain, K., McCarthy, J.K. and Tebo, B.M. Elimination of manganese(II,III) oxidation in Pseudomonas putida GB-1 by a double knockout of two putative multicopper oxidase genes. Appl. Environ. Microbiol. 79 (2013) 357-366. [PMID: 23124227]
5. Su, J., Bao, P., Bai, T., Deng, L., Wu, H., Liu, F. and He, J. CotA, a multicopper oxidase from Bacillus pumilus WH4, exhibits manganese-oxidase activity. PLoS One 8 (2013) e60573. [PMID: 23577125]
Accepted name: cuproxidase
Reaction: 4 Cu+ + 4 H+ + O2 = 4 Cu2+ + 2 H2O
Other name(s): cueO (gene name); cuprous oxidase; Cu(I) oxidase; copper efflux oxidase
Systematic name: copper(I):oxygen oxidoreductase
Comments: The enzyme, characterized from the bacterium Escherichia coli, is involved in copper tolerance under aerobic conditions. The enzyme contains a substrate binding (type 1) copper site and a trinuclear copper center (consisting of type 2 and type 3 copper sites) in which oxygen binding and reduction takes place. It also contains a methionine rich region that can bind additional copper ions. In vitro, if the substrate binding site is occupied by copper(II), the enzyme can function as a laccase-type quinol oxidase (EC 1.10.3.2) . However, in vivo this site is occupied by a copper(I) ion and the enzyme functions as a cuprous oxidase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Kim, C., Lorenz, W.W., Hoopes, J.T. and Dean, J.F. Oxidation of phenolate siderophores by the multicopper oxidase encoded by the Escherichia coli yacK gene. J. Bacteriol. 183 (2001) 4866-4875. [PMID: 11466290]
2. Grass, G. and Rensing, C. CueO is a multi-copper oxidase that confers copper tolerance in Escherichia coli, Biochem. Biophys. Res. Commun. 286 (2001) 902-908. [PMID: 11527384]
3. Outten, F.W., Huffman, D.L., Hale, J.A. and O'Halloran, T.V. The independent cue and cus systems confer copper tolerance during aerobic and anaerobic growth in Escherichia coli, J. Biol. Chem. 276 (2001) 30670-30677. [PMID: 11399769]
4. Roberts, S.A., Weichsel, A., Grass, G., Thakali, K., Hazzard, J.T., Tollin, G., Rensing, C. and Montfort, W.R. Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli, Proc. Natl. Acad. Sci. USA 99 (2002) 2766-2771. [PMID: 11867755]
5. Roberts, S.A., Wildner, G.F., Grass, G., Weichsel, A., Ambrus, A., Rensing, C. and Montfort, W.R. A labile regulatory copper ion lies near the T1 copper site in the multicopper oxidase CueO. J. Biol. Chem. 278 (2003) 31958-31963. [PMID: 12794077]
6. Singh, S.K., Grass, G., Rensing, C. and Montfort, W.R. Cuprous oxidase activity of CueO from Escherichia coli, J. Bacteriol. 186 (2004) 7815-7817. [PMID: 15516598]
7. Galli, I., Musci, G. and Bonaccorsi di Patti, M.C. Sequential reconstitution of copper sites in the multicopper oxidase CueO. J. Biol. Inorg. Chem. 9 (2004) 90-95. [PMID: 14648285]
8. Djoko, K.Y., Chong, L.X., Wedd, A.G. and Xiao, Z. Reaction mechanisms of the multicopper oxidase CueO from Escherichia coli support its functional role as a cuprous oxidase. J. Am. Chem. Soc. 132 (2010) 2005-2015. [PMID: 20088522]
9. Singh, S.K., Roberts, S.A., McDevitt, S.F., Weichsel, A., Wildner, G.F., Grass, G.B., Rensing, C. and Montfort, W.R. Crystal structures of multicopper oxidase CueO bound to copper(I) and silver(I): functional role of a methionine-rich sequence. J. Biol. Chem. 286 (2011) 37849-37857. [PMID: 21903583]
10. Cortes, L., Wedd, A.G. and Xiao, Z. The functional roles of the three copper sites associated with the methionine-rich insert in the multicopper oxidase CueO from E. coli, Metallomics 7 (2015) 776-785. [PMID: 25679350]
[EC 1.16.5.1 Transferred entry: ascorbate ferrireductase (transmembrane). Now EC 7.2.1.3, ascorbate ferrireductase (transmembrane) (EC 1.16.5.1 created 2011, deleted 2018)]
[EC 1.16.8.1 Deleted entry: cob(II)yrinic acid a,c-diamide reductase. This activity is now known to be catalyzed by EC 2.5.1.17, corrinoid adenosyltransferase (EC 1.16.8.1 created 2004, deleted 2019)]
EC 1.16.9.1
Accepted name: iron:rusticyanin reductase
Reaction: Fe(II) + rusticyanin = Fe(III) + reduced rusticyanin
Other name(s): Cyc2 (ambiguous)
Systematic name: Fe(II):rusticyanin oxidoreductase
Comments: Contains c-type heme, The enzyme in Acidithiobacillus ferrooxidans is a component of an electron transfer chain from Fe(II), comprising this enzyme, the copper protein rusticyanin, cytochrome c4, and cytochrome c oxidase (EC 7.1.1.9)
Links to other databases:
BRENDA,
EXPASY,
KEGG,
Metacyc,
CAS registry number:
References:
1. Blake, R.C., 2nd and Shute, E.A. Respiratory enzymes of Thiobacillus ferrooxidans. Kinetic properties of an acid-stable iron:rusticyanin oxidoreductase. Biochemistry 33 (1994) 9220-9228. [PMID: 8049223]
2. Appia-Ayme, C., Bengrine, A., Cavazza, C., Giudici-Orticoni, M.T., Bruschi, M., Chippaux, M. and Bonnefoy, V. Characterization and expression of the co-transcribed cyc1 and cyc2 genes encoding the cytochrome c4 (c552) and a high-molecular-mass cytochrome c from Thiobacillus ferrooxidans ATCC 33020. FEMS Microbiol. Lett. 167 (1998) 171-177. [PMID: 9809418]
3. Yarzabal, A., Brasseur, G., Ratouchniak, J., Lund, K., Lemesle-Meunier, D., DeMoss, J.A. and Bonnefoy, V. The high-molecular-weight cytochrome c Cyc2 of Acidithiobacillus ferrooxidans is an outer membrane protein. J. Bacteriol. 184 (2002) 313-317. [PMID: 11741873]
4. Yarzabal, A., Appia-Ayme, C., Ratouchniak, J. and Bonnefoy, V. Regulation of the expression of the Acidithiobacillus ferrooxidans rus operon encoding two cytochromes c, a cytochrome oxidase and rusticyanin. Microbiology 150 (2004) 2113-2123. [PMID: 15256554]
5. Taha, T.M., Kanao, T., Takeuchi, F. and Sugio, T. Reconstitution of iron oxidase from sulfur-grown Acidithiobacillus ferrooxidans. Appl. Environ. Microbiol. 74 (2008) 6808-6810. [PMID: 18791023]
6. Castelle, C., Guiral, M., Malarte, G., Ledgham, F., Leroy, G., Brugna, M. and Giudici-Orticoni, M.T. A new iron-oxidizing/O2-reducing supercomplex spanning both inner and outer membranes, isolated from the extreme acidophile Acidithiobacillus ferrooxidans. J. Biol. Chem. 283 (2008) 25803-25811. [PMID: 18632666]
7. Quatrini, R., Appia-Ayme, C., Denis, Y., Jedlicki, E., Holmes, D.S. and Bonnefoy, V. Extending the models for iron and sulfur oxidation in the extreme acidophile Acidithiobacillus ferrooxidans. BMC Genomics 10 (2009) 394. [PMID: 19703284]
EC 1.16.98 With other, known, physiological acceptor
EC 1.16.98.1 transferred now EC 1.16.9.1
EC 1.16.99.1
Accepted name: [Co(II) methylated amine-specific corrinoid protein] reductase
Reaction: (1) ATP + a [Co(II) methylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) methylamine-specific corrinoid protein] + acceptor
Glossary: ramA (gene name)
Systematic name: acceptor:[cobalt(II) methylated amines-specific corrinoid protein] oxidoreductase (ATP-hydrolysing)
Comments: Methyltrophic corrinoid proteins must have the cobalt atom in the active cobalt(I) state to become methylated. Because the cobalt(I)/cobalt(II) transformation has a very low redox potential the corrinoid cofactor is subject to adventitious oxidation to the cobalt(II) state, which renders the proteins inactive. This enzyme, characterized from the methanogenic archaeon Methanosarcina barkeri, reduces cobalt(II) back to cobalt(I), restoring activity. The enzyme acts on the corrinoid proteins involved in methanogenesis from methylamine, dimethylamine, and trimethylamine, namely MtmC, MtbC, and MttC, respectively. While in vitro the enzyme can use Ti(III)-citrate as the electron donor, the in vivo donor is not known. The enzyme from Methanosarcina barkeri contains a C-terminal [4Fe-4S] ferredoxin-like domain.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Ferguson, T., Soares, J.A., Lienard, T., Gottschalk, G. and Krzycki, J.A. RamA, a protein required for reductive activation of corrinoid-dependent methylamine methyltransferase reactions in methanogenic archaea. J. Biol. Chem. 284 (2009) 2285-2295. [PMID: 19043046]
2. Durichen, H., Diekert, G. and Studenik, S. Redox potential changes during ATP-dependent corrinoid reduction determined by redox titrations with europium(II)-DTPA. Protein Sci. 28 (2019) 1902-1908. [PMID: 31359509]
EC 1.17.1 With NAD+ or NADP+ as acceptor
EC 1.17.99 With unknown physiological acceptors
(2) ATP + a [Co(II) dimethylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) dimethylamine-specific corrinoid protein] + acceptor
(3) ATP + a [Co(II) trimethylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) trimethylamine-specific corrinoid protein] + acceptor
EC 1.17 ACTING ON CH or CH2 GROUPS
Sections
EC 1.17.3 With oxygen as acceptor
EC 1.17.4 With disulfide as acceptor
EC 1.17.5 With a quinone or similar compound as acceptor
EC 1.17.98 With other, known, physiological acceptors
EC 1.17.1 With NAD+ or NADP+ as acceptor
Accepted name: CDP-4-dehydro-6-deoxyglucose reductase
Reaction: CDP-4-dehydro-3,6-dideoxy-D-glucose + NAD(P)+ + H2O = CDP-4-dehydro-6-deoxy-D-glucose + NAD(P)H + H+
For diagram click here.
Other name(s): CDP-4-keto-6-deoxyglucose reductase; cytidine diphospho-4-keto-6-deoxy-D-glucose reductase; cytidine diphosphate 4-keto-6-deoxy-D-glucose-3-dehydrogenase; CDP-4-keto-deoxy-glucose reductase; CDP-4-keto-6-deoxy-D-glucose-3-dehydrogenase system; NAD(P)H:CDP-4-keto-6-deoxy-D-glucose oxidoreductase
Systematic name: CDP-4-dehydro-3,6-dideoxy-D-glucose:NAD(P)+ 3-oxidoreductase
Comments: The enzyme consists of two proteins. One forms an enzyme-bound adduct of the CDP-4-dehydro-6-deoxyglucose with pyridoxamine phosphate, in which the 3-hydroxy group has been removed. The second catalyses the reduction of this adduct by NAD(P)H and release of the CDP-4-dehydro-3,6-dideoxy-D-glucose and pyridoxamine phosphate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-87-4
References:
1. Pape, H. and Strominger, J.L. Enzymatic synthesis of cytidine diphosphate 3,6-dideoxyhexoses. V. Partial purification of the two protein components required for introduction of the 3-deoxy group. J. Biol. Chem. 244 (1969) 3598-3604. [PMID: 4389672]
2. Rubenstein, P.A. and Strominger, J.L. Enzymatic synthesis of cytidine diphosphate 3,6-dideoxyhexoses. VII. Mechanistic roles of enzyme E1 and pyridoxamine 5'-phosphate in the formation of cytidine diphosphate-4-keto-3,6-dideoxy-D-glucose from cytidine diphosphate-4-keto-6-deoxy-D-glucose. J. Biol. Chem. 249 (1974) 3776-3781. [PMID: 4152100]
3. Liu, H.-W. and Thorson, J.S. Pathways and mechanisms in the biogenesis of novel deoxysugars by bacteria. Annu. Rev. Microbiol. 48 (1994) 223-256. [PMID: 7826006]
[EC 1.17.1.2 Transferred entry: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, now classified as EC 1.17.7.4, 4-hydroxy-3-methylbut-2-enyl diphosphate reductase. (EC 1.17.1.2 created 2003, modified 2009, deleted 2016)]
Accepted name: leucoanthocyanidin reductase
Reaction: (2R,3S)-catechin + NADP+ + H2O = 2,3-trans-3,4-cis-leucocyanidin + NADPH + H+
For diagram click here.
Other name(s): leucocyanidin reductase
Systematic name: (2R,3S)-catechin:NADP+ 4-oxidoreductase
Comments: The enzyme catalyses the synthesis of catechin, catechin-4β-ol (leucocyanidin) and the related flavan-3-ols afzelechin and gallocatechin, which are initiating monomers in the synthesis of plant polymeric proanthocyanidins or condensed tannins. While 2,3-trans-3,4-cis-leucocyanidin is the preferred flavan-3,4-diol substrate, 2,3-trans-3,4-cis-leucodelphinidin and 2,3-trans-3,4-cis-leucopelargonidin can also act as substrates, but more slowly. NADH can replace NADPH but is oxidized more slowly.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 776323-46-7
References:
1. Tanner, G.J. and Kristiansen, K.N. Synthesis of 3,4-cis-[3H]leucocyanidin and enzymatic reduction to catechin. Anal. Biochem. 209 (1993) 274-277. [PMID: 8470799]
2. Tanner, G.J., Francki, K.T., Abrahams, S., Watson, J.M., Larkin, P.J. and Ashton, A.R. Proanthocyanidin biosynthesis in plants: Purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA. J. Biol. Chem. 278 (2003) 31647-31656. [PMID: 12788945]
Accepted name: xanthine dehydrogenase
Reaction: xanthine + NAD+ + H2O = urate + NADH + H+
For diagram of reaction click here
Glossary: 4-mercuribenzoate = (4-carboxylatophenyl)mercury
Other name(s): NAD+-xanthine dehydrogenase; xanthine-NAD+ oxidoreductase; xanthine/NAD+ oxidoreductase; xanthine oxidoreductase
Systematic name: xanthine:NAD+ oxidoreductase
Comments: Acts on a variety of purines and aldehydes, including hypoxanthine. The mammalian enzyme can also convert all-trans retinol to all-trans-retinoate, while the substrate is bound to a retinoid-binding protein [14]. The enzyme from eukaryotes contains [2Fe-2S], FAD and a molybdenum centre. The mammalian enzyme predominantly exists as the NAD-dependent dehydrogenase (EC 1.17.1.4). During purification the enzyme is largely converted to an O2-dependent form, xanthine oxidase (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [2,6,8,15] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [2,7,15].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9054-84-6
References:
1. Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133-138. [PMID: 6960894]
2. Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739-745. [PMID: 4342395]
3. Parzen, S.D. and Fox, A.S. Purification of xanthine dehydrogenase from Drosophila melanogaster. Biochim. Biophys. Acta 92 (1964) 465-471. [PMID: 14264879]
4. Rajagopalan, K.V. and Handler, P. Purification and properties of chicken liver xanthine dehydrogenase. J. Biol. Chem. 242 (1967) 4097-4107. [PMID: 4294045]
5. Smith, S.T., Rajagopalan, K.V. and Handler, P. Purification and properties of xanthine dehydroganase from Micrococcus lactilyticus. J. Biol. Chem. 242 (1967) 4108-4117. [PMID: 6061702]
6. Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254-260. [PMID: 3459393]
7. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564-1570. [PMID: 3294898]
8. Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O2-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179-183. [PMID: 2610112]
9. Parschat, K., Canne, C., Hüttermann, J., Kappl, R. and Fetzner, S. Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation-reduction potentials of its redox-active centers, and first EPR characterization. Biochim. Biophys. Acta 1544 (2001) 151-165. [PMID: 11341925]
10. Ichida, K., Amaya, Y., Noda, K., Minoshima, S., Hosoya, T., Sakai, O., Shimizu, N. and Nishino, T. Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene 133 (1993) 279-284. [PMID: 8224915]
11. Enroth, C., Eger, B.T., Okamoto, K., Nishino, T., Nishino, T. and Pai, E.F. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc. Natl. Acad. Sci. USA 97 (2000) 10723-10728. [PMID: 11005854]
12. Truglio, J.J., Theis, K., Leimkuhler, S., Rappa, R., Rajagopalan, K.V. and Kisker, C. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10 (2002) 115-125. [PMID: 11796116]
13. Hille, R. The mononuclear molybdenum enzymes. Chem. Rev. 96 (1996) 2757-2816. [PMID: 11848841]
14. Taibi, G., Di Gaudio, F. and Nicotra, C.M. Xanthine dehydrogenase processes retinol to retinoic acid in human mammary epithelial cells. J. Enzyme Inhib. Med. Chem. 23 (2008) 317-327. [PMID: 18569334]
15. Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278-3289. [PMID: 18513323]
Accepted name: nicotinate dehydrogenase
Reaction: nicotinate + H2O + NADP+ = 6-hydroxynicotinate + NADPH + H+
For diagram click here.
Other name(s): nicotinic acid hydroxylase; nicotinate hydroxylase
Systematic name: nicotinate:NADP+ 6-oxidoreductase (hydroxylating)
Comments: A flavoprotein containing non-heme iron. The enzyme is capable of acting on a variety of nicotinate analogues to varying degrees, including pyrazine-2-carboxylate, pyrazine 2,3-dicarboxylate, trigonelline and 6-methylnicotinate. The enzyme from Clostridium barkeri also possesses a catalytically essential, labile selenium that can be removed by reaction with cyanide.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9059-03-4
References:
1. Holcenberg, J.S. and Stadtman, E.R. Nicotinic acid metabolism. 3. Purification and properties of a nicotinic acid hydroxylase. J. Biol. Chem. 244 (1969) 1194-1203. [PMID: 4388026]
2. Gladyshev, V.N., Khangulov, S.V. and Stadtman, T.C. Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase from Clostridium barkeri. Biochemistry 35 (1996) 212-223. [PMID: 8555176]
3. Gladyshev, V.N., Khangulov, S.V. and Stadtman, T.C. Nicotinic-acid hydroxylase from Clostridium barkeri - electron-paramagnetic-resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme. Proc. Natl. Acad. Sci. USA 91 (1994) 232-236. [PMID: 8278371]
4. Dilworth, G.L. Occurrence of molybdenum in the nicotinic-acid hydroxylase from Clostridium barkeri. Arch. Biochem. Biophys. 221 (1983) 565-569. [PMID: 6838209]
5. Dilworth, G.L. Properties of the selenium-containing moiety of nicotinic-acid hydroxylase from Clostridium barkeri. Arch. Biochem. Biophys. 219 (1983) 30-38.
6. Nagel, M. and Andreesen, J.R. Purification and characterization of the molybdoenzymes nicotinate dehydrogenase and 6-hydroxynicotinate dehydrogenase from Bacillus niacini. Arch. Microbiol. 154 (1990) 605-613.
[EC 1.17.1.6 Transferred entry: now EC 1.17.99.5, bile-acid 7α-dehydroxylase. It is now known that FAD is the acceptor and not NAD+ as was thought previously. (EC 1.17.1.6 created 2005, deleted 2006)]
[EC 1.17.1.7 Transferred entry: 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase. Now EC 1.2.1.91, 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase (EC 1.17.1.7 created 2011, deleted 2014)]
Accepted name: 4-hydroxy-tetrahydrodipicolinate reductase
Reaction: (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + NAD(P)+ + H2O = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + NAD(P)H + H+
For diagram of reaction click here
Glossary: (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate
(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate = (2S)-2,3,4,5-tetrahydrodipicolinate
Other name(s): dihydrodipicolinate reductase (incorrect); dihydrodipicolinic acid reductase (incorrect); 2,3,4,5-tetrahydrodipicolinate:NAD(P)+ oxidoreductase (incorrect); dapB (gene name)
Systematic name: (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate:NAD(P)+ 4-oxidoreductase
Comments: The substrate of the enzyme was initially thought to be (S)-2,3-dihydrodipicolinate [1], and the enzyme was classified accordingly as EC 1.3.1.26, dihydrodipicolinate reductase. Later studies of the enzyme from the bacterium Escherichia coli have suggested that the actual substrate of the enzyme is (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate, and that its activity includes a dehydration step [2], and thus the enzyme has been reclassified as 4-hydroxy-tetrahydrodipicolinate reductase. However, the identity of the substrate is still controversial, as more recently it has been suggested that it may be (S)-2,3-dihydrodipicolinate after all [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Farkas, W. and Gilvarg, C. The reduction step in diaminopimelic acid biosynthesis. J. Biol. Chem. 240 (1965) 4717-4722. [PMID: 4378965]
2. Devenish, S.R., Blunt, J.W. and Gerrard, J.A. NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase. J. Med. Chem. 53 (2010) 4808-4812. [PMID: 20503968]
3. Karsten, W.E., Nimmo, S.A., Liu, J. and Chooback, L. Identification of 2,3-dihydrodipicolinate as the product of the dihydrodipicolinate synthase reaction from Escherichia coli. Arch. Biochem. Biophys. 653 (2018) 50-62. [PMID: 29944868]
Accepted name: formate dehydrogenase
Reaction: formate + NAD+ = CO2 + NADH
Other name(s): formate-NAD+ oxidoreductase; FDH I; FDH II; N-FDH; formic hydrogen-lyase; formate hydrogenlyase; hydrogenlyase; NAD+-linked formate dehydrogenase; NAD+-dependent formate dehydrogenase; formate dehydrogenase (NAD+); NAD+-formate dehydrogenase; formate benzyl-viologen oxidoreductase; formic acid dehydrogenase
Systematic name: formate:NAD+ oxidoreductase
Comments: The enzyme from most aerobic organisms is devoid of redox-active centres but that from the proteobacterium Methylosinus trichosporium contains iron-sulfur centres, flavin and a molybdenum centre [3]. Together with EC 1.12.1.2 hydrogen dehydrogenase, forms a system previously known as formate hydrogenlyase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Davison, D.C. Studies on plant formic dehydrogenase. Biochem. J. 49 (1951) 520-526. [PMID: 14886318]
2. Quayle, J.R. Formate dehydrogenase. Methods Enzymol. 9 (1966) 360-364.
3. Jollie, D.R. and Lipscomb, J.D. Formate dehydrogenase from Methylosinus trichosporium OB3b. Purification and spectroscopic characterization of the cofactors. J. Biol. Chem. 266 (1991) 21853-21863. [PMID: 1657982]
Accepted name: formate dehydrogenase (NADP+)
Reaction: formate + NADP+ = CO2 + NADPH
Other name(s): NADP+-dependent formate dehydrogenase
Systematic name: formate:NADP+ oxidoreductase
Comments: A tungsten-selenium-iron protein characterized from the bacterium Moorella thermoacetica. It is extremely sensitive to oxygen.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Andreesen, J.R. and Ljungdahl, L.G. Nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase from Clostridium thermoaceticum: purification and properties. J. Bacteriol. 120 (1974) 6-14. [PMID: 4154039]
2. Yamamoto, I., Saiki, T., Liu, S.-M. and Ljungdahl, L.G. Purification and properties of NADP-dependent formate dehydrogenase from Clostridium thermoaceticum, a tungsten-selenium-iron protein. J. Biol. Chem. 258 (1983) 1826-1832. [PMID: 6822536]
Accepted name: formate dehydrogenase (NAD+, ferredoxin)
Reaction: 2 formate + NAD+ + 2 oxidized ferredoxin [iron-sulfur] cluster = 2 CO2 + NADH + H+ + 2 reduced ferredoxin [iron-sulfur] cluster
Other name(s): electron-bifurcating formate dehydrogenase
Systematic name: formate:NAD+, ferredoxin oxidoreductase
Comments: The enzyme complex, isolated from the bacterium Gottschalkia acidurici, couples the reduction of NAD+ and the reduction of ferredoxin with formate via flavin-based electron bifurcation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Wang, S., Huang, H., Kahnt, J. and Thauer, R.K. Clostridium acidurici electron-bifurcating formate dehydrogenase. Appl. Environ. Microbiol. 79 (2013) 6176-6179. [PMID: 23872566]
Accepted name: nicotinate dehydrogenase (cytochrome)
Reaction: nicotinate + a ferricytochrome + H2O = 6-hydroxynicotinate + a ferrocytochrome
Other name(s): nicotinic acid hydroxylase; nicotinate hydroxylase
Systematic name: nicotinate:cytochrome 6-oxidoreductase (hydroxylating)
Comments: This two-component enzyme from Pseudomonas belongs to the family of xanthine dehydrogenases, but differs from most other members of this family. While most members contain an FAD cofactor, the large subunit of this enzyme contains three c-type cytochromes, enabling it to interact with the electron transfer chain, probably by delivering the electrons to a cytochrome oxidase. The small subunit contains a typical molybdopterin cytosine dinucleotide(MCD) cofactor and two [2Fe-2S] clusters [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Jimenez, J.I., Canales, A., Jimenez-Barbero, J., Ginalski, K., Rychlewski, L., Garcia, J.L. and Diaz, E. Deciphering the genetic determinants for aerobic nicotinic acid degradation: the nic cluster from Pseudomonas putida KT2440. Proc. Natl. Acad. Sci. USA 105 (2008) 11329-11334. [PMID: 18678916]
2. Yang, Y., Yuan, S., Chen, T., Ma, P., Shang, G. and Dai, Y. Cloning, heterologous expression, and functional characterization of the nicotinate dehydrogenase gene from Pseudomonas putida KT2440. Biodegradation 20 (2009) 541-549. [PMID: 19118407]
Accepted name: lupanine 17-hydroxylase (cytochrome c)
Reaction: lupanine + 2 ferricytochrome c + H2O = 17-hydroxylupanine + 2 ferrocytochrome c + 2 H+
Other name(s): lupanine dehydrogenase (cytochrome c)
Systematic name: lupanine:cytochrome c-oxidoreductase (17-hydroxylating)
Comments: The enzyme isolated from Pseudomonas putida contains heme c and requires pyrroloquinoline quinone (PQQ) for activity
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Hopper, D.J., Rogozinski, J. and Toczko, M. Lupanine hydroxylase, a quinocytochrome c from an alkaloid-degrading Pseudomonas sp. Biochem. J. 279 (1991) 105-109. [PMID: 1656935]
2. Hopper, D.J. and Kaderbhai, M.A. The quinohaemoprotein lupanine hydroxylase from Pseudomonas putida. Biochim. Biophys. Acta 1647 (2003) 110-115. [PMID: 12686118]
Accepted name: formate dehydrogenase (cytochrome-c-553)
Reaction: formate + 2 ferricytochrome c-553 = CO2 + 2 ferrocytochrome c-553 + H+
Systematic name: formate:ferricytochrome-c-553 oxidoreductase
Comments: The enzyme has been characterized from the bacterium Desulfovibrio vulgaris. In vitro, yeast cytochrome c, ferricyanide and phenazine methosulfate can act as acceptors.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Yagi, T. Formate: cytochrome oxidoreductase of Desulfovibrio vulgaris. J. Biochem. (Tokyo) 66 (1969) 473-478. [PMID: 4982127]
2. Yagi, T. Purification and properties of cytochrome c-553, an electron acceptor for formate dehydrogenase of Desulfovibrio vulgaris, Miyazaki. Biochim. Biophys. Acta 548 (1979) 96-105. [PMID: 226135]
Accepted name: pteridine oxidase
Reaction: 2-amino-4-hydroxypteridine + O2 = 2-amino-4,7-dihydroxypteridine + (?)
Systematic name: 2-amino-4-hydroxypteridine:oxygen oxidoreductase (7-hydroxylating)
Comments: Different from EC 1.17.3.2 xanthine oxidase; does not act on hypoxanthine.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 74082-65-8
References:
1. Yong, Y.-N. Detection of a pteridine oxidase in plants. Plant Sci. Lett. 18 (1980) 169-175.
Accepted name: xanthine oxidase
Reaction: xanthine + H2O + O2 = urate + H2O2
For diagram of reaction, click here
Glossary: 4-mercuribenzoate = (4-carboxylatophenyl)mercury
Other name(s): hypoxanthine oxidase; hypoxanthine:oxygen oxidoreductase; Schardinger enzyme; xanthine oxidoreductase; hypoxanthine-xanthine oxidase; xanthine:O2 oxidoreductase; xanthine:xanthine oxidase
Systematic name: xanthine:oxygen oxidoreductase
Comments: An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 O2.- + 2 H+. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O2-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9002-17-9
References:
1. Avis, P.G., Bergel, F. and Bray, R.C. Cellular constituents. The chemistry of xanthine oxidase. Part I. The preparation of a crystalline xanthine oxidase from cow's milk. J. Chem. Soc. (Lond.) (1955) 1100-1105.
2. Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133-138. [PMID: 6960894]
3. Bray, R.C. Xanthine oxidase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 533-556.
4. Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739-745. [PMID: 4342395]
5. Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254-260. [PMID: 3459393]
6. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564-1570. [PMID: 3294898]
7. Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O2-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179-183. [PMID: 2610112]
8. Carpani, G., Racchi, M., Ghezzi, P., Terao, M. and Garattini, E. Purification and characterization of mouse liver xanthine oxidase. Arch. Biochem. Biophys. 279 (1990) 237-241. [PMID: 2350174]
9. Eger, B.T., Okamoto, K., Enroth, C., Sato, M., Nishino, T., Pai, E.F. and Nishino, T. Purification, crystallization and preliminary X-ray diffraction studies of xanthine dehydrogenase and xanthine oxidase isolated from bovine milk. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 1656-1658. [PMID: 11092937]
10. Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278-3289. [PMID: 18513323]
Accepted name: 6-hydroxynicotinate dehydrogenase
Reaction: 6-hydroxynicotinate + H2O + O2 = 2,6-dihydroxynicotinate + H2O2
Other name(s): 6-hydroxynicotinic acid hydroxylase; 6-hydroxynicotinic acid dehydrogenase; 6-hydroxynicotinate hydroxylase; 6-hydroxynicotinate:O2 oxidoreductase
Systematic name: 6-hydroxynicotinate:oxygen oxidoreductase
Comments: Contains [2Fe-2S] iron-sulfur centres, FAD and molybdenum. It also has a catalytically essential, labile selenium that can be removed by reaction with cyanide. In Bacillus niacini, this enzyme is required for growth on nicotinic acid.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 122191-32-6
References:
1. Nagel, M. and Andreesen, J.R. Molybdenum-dependent degradation of nicotinic acid by Bacillus sp. DSM 2923. FEMS Microbiol. Lett. 59 (1989) 147-152.
2. Nagel, M. and Andreesen, J.R. Purification and characterization of the molybdoenzymes nicotinate dehydrogenase and 6-hydroxynicotinate dehydrogenase from Bacillus niacini. Arch. Microbiol. 154 (1990) 605-613.
Accepted name: juglone 3-hydroxylase
Reaction: 2 juglone + O2 = 2 3,5-dihydroxy-1,4-naphthoquinone (overall reaction)
(1a) 2 juglone + 2 H2O = 2 naphthalene-1,2,4,8-tetrol
(1b) 2 naphthalene-1,2,4,8-tetrol + O2 = 2 3,5-dihydroxy-1,4-naphthoquinone + 2 H2O
Glossary: juglone = 5-hydroxy-1,4-naphthoquinone
Other name(s): juglone hydroxylase; naphthoquinone hydroxylase; naphthoquinone-hydroxylase
Systematic name: 5-hydroxy-1,4-naphthoquinone,water:oxygen oxidoreductase (3-hydroxylating)
Comments: Even though oxygen is consumed, molecular oxygen is not incorporated into the product. Catalysis starts by incorporation of an oxygen atom from a water molecule into the substrate. The naphthalene-1,2,4,8-tetrol intermediate is then oxidized by molecular oxygen, which is reduced to water. Also acts on 1,4-naphthoquinone, naphthazarin and 2-chloro-1,4-naphthoquinone.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Rettenmaier, H. and Lingens, F. Purification and some properties of two isofunctional juglone hydroxylases from Pseudomonas putida J1. Biol. Chem. Hoppe-Seyler 366 (1985) 637-646. [PMID: 4041238]
Accepted name: 4-oxocyclohexanecarboxylate 2-dehydrogenase
Reaction: 4-oxocyclohexane-1-carboxylate + O2 = 4-oxocyclohex-2-ene-1-carboxylate + H2O2
Glossary: 4-oxocyclohexane-1-carboxylate = 4-oxocyclohexanecarboxylate
Other name(s): chcC1 (gene name); 4-oxocyclohexanecarboxylate desaturase I; 4-oxocyclohexanecarboxylate 2-desaturase
Systematic name: 4-oxocyclohexane-1-carboxylate:oxygen oxidoreductase (4-oxocyclohex-2-ene-1-carboxylate-forming)
Comments: Contains FAD. The enzyme, characterized from the bacterium Corynebacterium cyclohexanicum, participates in a cyclohexane-1-carboxylate degradation pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Kaneda, T., Obata, H. and Tokumoto, M. Aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid by two distinctive desaturases from Corynebacterium cyclohexanicum. Properties of two desaturases. Eur. J. Biochem. 218 (1993) 997-1003. [PMID: 8281951]
2. Yamamoto, T., Hasegawa, Y., Lau, P.CK. and Iwaki, H. Identification and characterization of a chc gene cluster responsible for the aromatization pathway of cyclohexanecarboxylate degradation in Sinomonas cyclohexanicum ATCC 51369. J. Biosci. Bioeng. 132 (2021) 621-629. [PMID: 34583900]
Accepted name: ribonucleoside-diphosphate reductase
Reaction: 2'-deoxyribonucleoside 5'-diphosphate + thioredoxin disulfide + H2O = ribonucleoside 5'-diphosphate + thioredoxin
Other name(s): ribonucleotide reductase (ambiguous); CDP reductase; ribonucleoside diphosphate reductase; UDP reductase; ADP reductase; nucleoside diphosphate reductase; ribonucleoside 5'-diphosphate reductase; ribonucleotide diphosphate reductase; 2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase; RR; nrdB (gene name); nrdF (gene name); nrdJ (gene name)
Systematic name: 2'-deoxyribonucleoside-5'-diphosphate:thioredoxin-disulfide 2'-oxidoreductase
Comments: This enzyme is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. There are three types of this enzyme differing in their cofactors. Class Ia enzymes contain a diiron(III)-tyrosyl radical, class Ib enzymes contain a dimanganese-tyrosyl radical, and class II enzymes contain adenosylcobalamin. In all cases the cofactors are involved in generation of a transient thiyl radical on a cysteine residue, which attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate) and EC 1.17.4.2, ribonucleoside-triphosphate reductase (thioredoxin).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9047-64-7
References:
1. Larsson, A. and Reichard, P. Enzymatic synthesis of deoxyribonucleotides. IX. Allosteric effects in the reduction of pyrimidine ribonucleotides by the ribonucleoside diphosphate reductase system of Escherichia coli. J. Biol. Chem. 241 (1966) 2533-2539. [PMID: 5330119]
2. Larsson, A. and Reichard, P. Enzymatic synthesis of deoxyribonucleotides. X. Reduction of purine ribonucleotides; allosteric behavior and substrate specificity of the enzyme system from Escherichia coli B. J. Biol. Chem. 241 (1966) 2540-2549. [PMID: 5330120]
3. Moore, E.C. and Hurlbert, R.B. Regulation of mammalian deoxyribonucleotide biosynthesis by nucleotides as activators and inhibitors. J. Biol. Chem. 241 (1966) 4802-4809. [PMID: 5926184]
4. Larsson, A. Ribonucleotide reductase from regenerating rat liver. II. Substrate phosphorylation level and effect of deoxyadenosine triphosphate. Biochim. Biophys. Acta 324 (1973) 447-451. [PMID: 4543472]
5. Lammers, M. and Follmann, H. The ribonucleotide reductases - a unique group of metalloenzymes essential for cell-proliferation. Struct. Bonding 54 (1983) 27-91.
6. Stubbe, J., Ator, M. and Krenitsky, T. Mechanism of ribonucleoside diphosphate reductase from Escherichia coli. Evidence for 3'-C--H bond cleavage. J. Biol. Chem. 258 (1983) 1625-1631. [PMID: 6337142]
7. Lenz, R. and Giese, B. Studies on the Mechanism of Ribonucleotide Reductases. J. Am. Chem. Soc. 119 (1997) 2784-2794.
8. Lawrence, C.C., Bennati, M., Obias, H.V., Bar, G., Griffin, R.G. and Stubbe, J. High-field EPR detection of a disulfide radical anion in the reduction of cytidine 5'-diphosphate by the E441Q R1 mutant of Escherichia coli ribonucleotide reductase. Proc. Natl. Acad. Sci. USA 96 (1999) 8979-8984. [PMID: 10430881]
9. Qiu, W., Zhou, B., Darwish, D., Shao, J. and Yen, Y. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem. Biophys. Res. Commun. 340 (2006) 428-434. [PMID: 16376858]
Accepted name: ribonucleoside-triphosphate reductase (thioredoxin)
Reaction: 2'-deoxyribonucleoside 5'-triphosphate + thioredoxin disulfide + H2O = ribonucleoside 5'-triphosphate + thioredoxin
Other name(s): ribonucleotide reductase (ambiguous); 2'-deoxyribonucleoside-triphosphate:oxidized-thioredoxin 2'-oxidoreductase
Systematic name: 2'-deoxyribonucleoside-5'-triphosphate:thioredoxin-disulfide 2'-oxidoreductase
Comments: The enzyme, characterized from the bacterium Lactobacillus leichmannii, is similar to class II ribonucleoside-diphosphate reductase (cf. EC 1.17.4.1). However, it is specific for the triphosphate versions of its substrates. The enzyme contains an adenosylcobalamin cofactor that is involved in generation of a transient thiyl (sulfanyl)radical on a cysteine residue. This radical attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl (α-oxoalkyl) radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9068-66-0
References:
1. Blakley, R.L. Cobamides and ribonucleotide reduction. I. Cobamide stimulation of ribonucleotide reduction in extracts of Lactobacillus leichmannii. J. Biol. Chem. 240 (1965) 2173-2180. [PMID: 14299643]
2. Goulian, M. and Beck, W.S. Purification and properties of cobamide-dependent ribonucleotide reductase from Lactobacillus leichmannii. J. Biol. Chem. 241 (1966) 4233-4242. [PMID: 5924645]
3. Stubbe, J., Ackles, D., Segal, R. and Blakley, R.L. On the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii. Evidence for 3' C--H bond cleavage. J. Biol. Chem. 256 (1981) 4843-4846. [PMID: 7014560]
4. Ashley, G.W., Harris, G. and Stubbe, J. The mechanism of Lactobacillus leichmannii ribonucleotide reductase. Evidence for 3' carbon-hydrogen bond cleavage and a unique role for coenzyme B12. J. Biol. Chem. 261 (1986) 3958-3964. [PMID: 3512563]
5. Lawrence, C.C. and Stubbe, J. The function of adenosylcobalamin in the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii. Curr. Opin. Chem. Biol. 2 (1998) 650-655. [PMID: 9818192]
6. Licht, S.S., Booker, S. and Stubbe, J. Studies on the catalysis of carbon-cobalt bond homolysis by ribonucleoside triphosphate reductase: evidence for concerted carbon-cobalt bond homolysis and thiyl radical formation. Biochemistry 38 (1999) 1221-1233. [PMID: 9930982]
[EC 1.17.4.3 Transferred entry: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase. As ferredoxin and not protein-disulfide is now known to take part in the reaction, the enzyme has been transferred to EC 1.17.7.1, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase. (EC 1.17.4.3 created 2003, deleted 2009)]
Accepted name: vitamin-K-epoxide reductase (warfarin-sensitive)
Reaction: (1) phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues
(2) phylloquinol + a protein with a disulfide bond = phylloquinone + a protein with reduced L-cysteine residues
For diagram of reaction click here
Glossary: phylloquinone = vitamin K1 = 2-methyl-3-phytyl-1,4-naphthoquinone
2,3-epoxyphylloquinone = vitamin K1 2,3-epoxide = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone
Other name(s): VKORC1 (gene name); VKORC1L1 (gene name)
Systematic name: phylloquinone:disulfide oxidoreductase
Comments: The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC 4.1.1.90, peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC 5.3.4.1, protein disulfide-isomerase, which transfers the required electrons from newly-synthesized proteins by catalysing the formation of disulfide bridges. The enzyme acts on the epoxide forms of both phylloquinone (vitamin K1) and menaquinone (vitamin K2). Inhibited strongly by (S)-warfarin and ferulenol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 55963-40-1
References:
1. Whitlon, D.S., Sadowski, J.A. and Suttie, J.W. Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17 (1978) 1371-1377. [PMID: 646989]
2. Lee, J.L. and Fasco, M.J. Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide. Biochemistry 23 (1984) 2246-2252. [PMID: 6733086]
3. Mukharji, I. and Silverman, R.B. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone. Proc. Natl. Acad. Sci. USA 82 (1985) 2713-2717. [PMID: 3857611]
4. Li, T., Chang, C.Y., Jin, D.Y., Lin, P.J., Khvorova, A. and Stafford, D.W. Identification of the gene for vitamin K epoxide reductase. Nature 427 (2004) 541-544. [PMID: 14765195]
5. Wajih, N., Hutson, S.M. and Wallin, R. Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction. J. Biol. Chem 282 (2007) 2626-2635. [PMID: 17124179]
6. Spohn, G., Kleinridders, A., Wunderlich, F.T., Watzka, M., Zaucke, F., Blumbach, K., Geisen, C., Seifried, E., Muller, C., Paulsson, M., Bruning, J.C. and Oldenburg, J. VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb Haemost 101 (2009) 1044-1050. [PMID: 19492146]
7. Schulman, S., Wang, B., Li, W. and Rapoport, T.A. Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners. Proc. Natl Acad. Sci. USA 107 (2010) 15027-15032. [PMID: 20696932]
Accepted name: vitamin-K-epoxide reductase (warfarin-insensitive)
Reaction: 3-hydroxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + 1,4-dithiothreitol
Glossary: 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone = vitamin K 2,3-epoxide
Systematic name: 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone:oxidized-dithiothreitol oxidoreductase
Comments: Vitamin K 2,3-epoxide is reduced to 3-hydroxy- (and 2-hydroxy-) vitamin K by 1,4-dithiothreitol, which is oxidized to a disulfide. Not inhibited by warfarin [cf. EC 1.17.4.4, vitamin-K-epoxide reductase (warfarin-sensitive)].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Mukharji, I. and Silverman, R.B. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone. Proc. Natl. Acad. Sci. USA 82 (1985) 2713-2717. [PMID: 3857611]
EC 1.17.5.2 caffeine dehydrogenase
EC 1.17.5.3 formate dehydrogenase-N
Accepted name: phenylacetyl-CoA dehydrogenase
Reaction: phenylacetyl-CoA + H2O + 2 quinone = phenylglyoxylyl-CoA + 2 quinol
For diagram of reaction click here.
Other name(s): phenylacetyl-CoA:acceptor oxidoreductase
Systematic name: phenylacetyl-CoA:quinone oxidoreductase
Comments: The enzyme from Thauera aromatica is a membrane-bound molybdenum—iron—sulfur protein. The enzyme is specific for phenylacetyl-CoA as substrate. Phenylacetate, acetyl-CoA, benzoyl-CoA, propanoyl-CoA, crotonyl-CoA, succinyl-CoA and 3-hydroxybenzoyl-CoA cannot act as substrates. The oxygen atom introduced into the product, phenylglyoxylyl-CoA, is derived from water and not molecular oxygen. Duroquinone, menaquinone and 2,6-dichlorophenolindophenol (DCPIP) can act as acceptor, but the likely physiological acceptor is ubiquinone [1]. A second enzyme, EC 3.1.2.25, phenylacetyl-CoA hydrolase, converts the phenylglyoxylyl-CoA formed into phenylglyoxylate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 210756-43-7
References:
1. Rhee, S.K. and Fuchs, G. Phenylacetyl-CoA:acceptor oxidoreductase, a membrane-bound molybdenum-iron-sulfur enzyme involved in anaerobic metabolism of phenylalanine in the denitrifying bacterium Thauera aromatica. Eur. J. Biochem. 262 (1999) 507-515. [PMID: 10336636]
2. Schneider, S. and Fuchs, G. Phenylacetyl-CoA:acceptor oxidoreductase, a new α-oxidizing enzyme that produces phenylglyoxylate. Assay, membrane localization, and differential production in Thauera aromatica. Arch. Microbiol. 169 (1998) 509-516. [PMID: 9575237]
Accepted name: caffeine dehydrogenase
Reaction: caffeine + ubiquinone + H2O = 1,3,7-trimethylurate + ubiquinol
Glossary: caffeine = 1,3,7-trimethylxanthine
Systematic name: caffeine:ubiquinone oxidoreductase
Comments: This enzyme, characterized from the soil bacterium Pseudomonas sp. CBB1, catalyses the incorporation of an oxygen atom originating from a water molecule into position C-8 of caffeine. It can also use theobromine as substrate. The enzyme utilizes short-tail ubiquinones as the preferred electron acceptor.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Yu, C.L., Kale, Y., Gopishetty, S., Louie, T.M. and Subramanian, M. A novel caffeine dehydrogenase in Pseudomonas sp. strain CBB1 oxidizes caffeine to trimethyluric acid. J. Bacteriol. 190 (2008) 772-776. [PMID: 17981969]
Accepted name: formate dehydrogenase-N
Reaction: formate + a quinone = CO2 + a quinol
Other name(s): Fdh-N; FdnGHI; nitrate-inducible formate dehydrogenase; formate dehydrogenase N; FDH-N; nitrate inducible Fdn; nitrate inducible formate dehydrogenase
Systematic name: formate:quinone oxidoreductase
Comments: The enzyme contains molybdopterin-guanine dinucleotides, five [4Fe-4S] clusters and two heme b groups. Formate dehydrogenase-N oxidizes formate in the periplasm, transferring electrons via the menaquinone pool in the cytoplasmic membrane to a dissimilatory nitrate reductase (EC 1.7.5.1), which transfers electrons to nitrate in the cytoplasm. The system generates proton motive force under anaerobic conditions [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Enoch, H.G. and Lester, R.L. The purification and properties of formate dehydrogenase and nitrate reductase from Escherichia coli. J. Biol. Chem. 250 (1975) 6693-6705. [PMID: 1099093]
2. Jormakka, M., Tornroth, S., Byrne, B. and Iwata, S. Molecular basis of proton motive force generation: structure of formate dehydrogenase-N. Science 295 (2002) 1863-1868. [PMID: 11884747]
3. Jormakka, M., Tornroth, S., Abramson, J., Byrne, B. and Iwata, S. Purification and crystallization of the respiratory complex formate dehydrogenase-N from Escherichia coli. Acta Crystallogr. D Biol. Crystallogr. 58 (2002) 160-162. [PMID: 11752799]
Accepted name: (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin)
Reaction: (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + H2O + 2 oxidized ferredoxin = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + 2 reduced ferredoxin
For diagram of reaction click here.
Other name(s): 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ambiguous); (E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:protein-disulfide oxidoreductase (hydrating) (incorrect); (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (ambiguous); gcpE (gene name); ISPG (gene name); (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase
Systematic name: (E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:oxidized ferredoxin oxidoreductase
Comments: An iron-sulfur protein found in plant chloroplasts and cyanobacteria that contains a [4Fe-4S] cluster [1]. Forms part of an alternative non-mevalonate pathway for isoprenoid biosynthesis [3]. Bacteria have a similar enzyme that uses flavodoxin rather than ferredoxin (cf. EC 1.17.7.3). The enzyme from the plant Arabidopsis thaliana is active with photoreduced 5-deazaflavin but not with flavodoxin [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Okada, K. and Hase, T. Cyanobacterial non-mevalonate pathway: (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase interacts with ferredoxin in Thermosynechococcus elongatus BP-1. J. Biol. Chem. 280 (2005) 20672-20679. [PMID: 15792953]
2. Seemann, M., Wegner, P., Schünemann, V., Tse Sum Bui, B., Wolff, M., Marquet, A., Trautwein, A.X. and Rohmer, M. Isoprenoid biosynthesis in chloroplasts via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE) from Arabidopsis thaliana is a [4Fe-4S] protein. J. Biol. Inorg. Chem. 10 (2005) 131-137. [PMID: 15650872]
3. Seemann, M., Tse Sum Bui, B., Wolff, M., Tritsch, D., Campos, N., Boronat, A., Marquet, A. and Rohmer, M. Isoprenoid biosynthesis through the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE) is a [4Fe-4S] protein. Angew. Chem. Int. Ed. Engl. 41 (2002) 4337-4339. [PMID: 12434382]
4. Seemann, M., Tse Sum Bui, B., Wolff, M., Miginiac-Maslow, M. and Rohmer, M. Isoprenoid biosynthesis in plant chloroplasts via the MEP pathway: direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG. FEBS Lett. 580 (2006) 1547-1552. [PMID: 16480720]
Accepted name: 7-hydroxymethyl chlorophyll a reductase
Reaction: chlorophyll a + H2O + 2 oxidized ferredoxin = 71-hydroxychlorophyll a + 2 reduced ferredoxin + 2 H+
For diagram of reaction click here
Glossary: 71-hydroxychlorophyll-a = 7-hydroxymethyl-chlorophyll a
Other name(s): HCAR; 71-hydroxychlorophyll-a:ferredoxin oxidoreductase
Systematic name: 71-hydroxychlorophyll a:ferredoxin oxidoreductase
Comments: Contains FAD and an iron-sulfur center. This enzyme, which is present in plant chloroplasts, carries out the second step in the conversion of chlorophyll b to chlorophyll a (cf. It similarly reduces chlorophyllide a.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Meguro, M., Ito, H., Takabayashi, A., Tanaka, R. and Tanaka, A. Identification of the 7-hydroxymethyl chlorophyll a reductase of the chlorophyll cycle in Arabidopsis. Plant Cell 23 (2011) 3442-3453. [PMID: 21934147]
Accepted name: (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin)
Reaction: (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + H2O + oxidized flavodoxin = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + reduced flavodoxin
For diagram of reaction click here.
Other name(s): 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ambiguous); (E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:protein-disulfide oxidoreductase (hydrating) (incorrect); (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (ambiguous); ispG (gene name)
Systematic name: (E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:oxidized flavodoxin oxidoreductase
Comments: A bacterial iron-sulfur protein that contains a [4Fe-4S] cluster. Forms part of an alternative non-mevalonate pathway for isoprenoid biosynthesis that is found in most bacteria. Plants and cyanobacteria have a similar enzyme that utilizes ferredoxin rather than flavodoxin (cf. EC 1.17.7.1).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Hecht, S., Eisenreich, W., Adam, P., Amslinger, S., Kis, K., Bacher, A., Arigoni, D. and Rohdich, F. Studies on the nonmevalonate pathway to terpenes: the role of the GcpE (IspG) protein. Proc. Natl. Acad. Sci. USA 98 (2001) 14837-14842. [PMID: 11752431]
2. Zepeck, F., Grawert, T., Kaiser, J., Schramek, N., Eisenreich, W., Bacher, A. and Rohdich, F. Biosynthesis of isoprenoids. purification and properties of IspG protein from Escherichia coli. J. Org. Chem. 70 (2005) 9168-9174. [PMID: 16268586]
3. Puan, K.J., Wang, H., Dairi, T., Kuzuyama, T. and Morita, C.T. fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. FEBS Lett 579 (2005) 3802-3806. [PMID: 15978585]
] Accepted name: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase
Reaction: (1) isopentenyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+
(2) dimethylallyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+
For diagram of reaction click here.
Glossary: isopentenyl = 3-methylbut-3-en-1-yl
prenyl = 3-methylbut-2-en-1-yl
Other name(s): isopentenyl-diphosphate:NADP+ oxidoreductase; LytB; (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase; HMBPP reductase; IspH; LytB/IspH; isopentenyl-diphosphate:ferredoxin oxidoreductase
Systematic name: 3-methylbut-3-en-1-yl-diphosphate:ferredoxin oxidoreductase
Comments: An iron-sulfur protein that contains an unusual [4Fe-4S] cluster [5,6]. This enzyme forms a system with a ferredoxin or a flavodoxin and an NAD(P)H-dependent reductase. This is the last enzyme in the non-mevalonate pathway for isoprenoid biosynthesis. This pathway, also known as the 1-deoxy-D-xylulose 5-phosphate (DOXP) or as the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, is found in most bacteria and in plant chloroplasts. The enzyme acts in the reverse direction, producing a 5:1 mixture of 3-methylbut-3-en-1-yl diphosphate and prenyl diphosphate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Rohdich, F., Hecht, S., Gärtner, K., Adam, P., Krieger, C., Amslinger, S., Arigoni, D., Bacher, A. and Eisenreich, W. Studies on the nonmevalonate terpene biosynthetic pathway: Metabolic role of IspH (LytB) protein. Proc. Natl. Acad. Sci. USA 99 (2002) 1158-1163. [PMID: 11818558]
2. Hintz, M., Reichenberg, A., Altincicek, B., Bahr, U., Gschwind, R.M., Kollas, A.-K., Beck, E., Wiesner, J., Eberl, M. and Jomaa, H. Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human T cells in Escherichia coli, FEBS Lett. 509 (2001) 317-322. [PMID: 11741609]
3. Charon, L., Pale-Grosdemange, C. and Rohmer, M. On the reduction steps in the mevalonate independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in the bacterium Zymomonas mobilis, Tetrahedron Lett. 40 (1999) 7231-7234.
4. Röhrich, R.C., Englert, N., Troschke, K., Reichenberg, A., Hintz, M., Seeber, F., Balconi, E., Aliverti, A., Zanetti, G., Köhler, U., Pfeiffer, M., Beck, E., Jomaa, H. and Wiesner, J. Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum, FEBS Lett. 579 (2005) 6433-6438. [PMID: 16289098]
5. Wolff, M., Seemann, M., Bui, T.S.B., Frapart, Y., Tritsch, D., Garcia Estrabot, A., Rodríguez-Concepción, M., Boronat, A., Marquet, A. and Rohmer, M. Isoprenoid biosynthesis via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH) from Escherichia coli is a [4Fe-4S] protein. FEBS Lett. 541 (2003) 115-120. [PMID: 12706830]
6. Faus, I., Reinhard, A., Rackwitz, S., Wolny, J.A., Schlage, K., Wille, H.C., Chumakov, A., Krasutsky, S., Chaignon, P., Poulter, C.D., Seemann, M. and Schunemann, V. Isoprenoid biosynthesis in pathogenic bacteria: nuclear resonance vibrational spectroscopy provides insight into the unusual [4Fe-4S] cluster of the E. coli LytB/IspH protein. Angew. Chem. Int. Ed. Engl. 54 (2015) 12584–12587. [PMID: 26118554]
EC 1.17.8.1
Accepted name: hydroxysqualene dehydroxylase
Reaction: squalene + FAD + H2O = hydroxysqualene + FADH2
Glossary: hydroxysqualene = (6E,10E,12R,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-12-ol
Other name(s): hpnE (gene name)
Systematic name: squalene:FAD oxidoreductase (hydroxylating)
Comments: This enzyme, isolated from the bacteria Rhodopseudomonas palustris and Zymomonas mobilis, participates, along with EC 2.5.1.103, presqualene diphosphate synthase, and EC 4.2.3.156, hydroxysqualene synthase, in the conversion of all-trans-farnesyl diphosphate to squalene. Eukaryotes achieve the same goal in a single step, catalysed by EC 2.5.1.21, squalene synthase.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Pan, J.J., Solbiati, J.O., Ramamoorthy, G., Hillerich, B.S., Seidel, R.D., Cronan, J.E., Almo, S.C. and Poulter, C.D. Biosynthesis of squalene from farnesyl diphosphate in bacteria: three steps catalyzed by three enzymes. ACS Cent Sci 1 (2015) 77-82. [PMID: 26258173]
EC 1.17.9 With a copper protein as acceptor
Accepted name: 4-methylphenol dehydrogenase (hydroxylating)
Reaction: 4-methylphenol + 4 oxidized azurin + H2O = 4-hydroxybenzaldehyde + 4 reduced azurin + 4 H+ (overall reaction)
(1a) 4-methylphenol + 2 oxidized azurin + H2O = 4-hydroxybenzyl alcohol + 2 reduced azurin + 2 H+
(1b) 4-hydroxybenzyl alcohol + 2 oxidized azurin = 4-hydroxybenzaldehyde + 2 reduced azurin + 2 H+
Glossary: 4-methylphenol = 4-cresol = p-cresol
Other name(s): pchCF (gene names); p-cresol-(acceptor) oxidoreductase (hydroxylating); p-cresol methylhydroxylase; 4-cresol dehydrogenase (hydroxylating)
Systematic name: 4-methylphenol:oxidized azurin oxidoreductase (methyl-hydroxylating)
Comments: This bacterial enzyme contains a flavin (FAD) subunit and a cytochrome c subunit. The flavin subunit abstracts two hydrogen atoms from the substrate, forming a quinone methide intermediate, then hydrates the latter at the benzylic carbon with a hydroxyl group derived from water. The protons are lost to the bulk solvent, while the electrons are passed to the heme on the cytochrome subunit, and from there to azurin, a small copper-binding protein that is co-localized with the enzyme in the periplasm. The first hydroxylation forms 4-hydroxybenzyl alcohol; a second hydroxylation converts this into 4-hydroxybenzaldehyde.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Hopper, D.J. and Taylor, D.G. The purification and properties of p-cresol-(acceptor) oxidoreductase (hydroxylating), a flavocytochrome from Pseudomonas putida. Biochem. J. 167 (1977) 155-162. [PMID: 588247]
2. McIntire, W., Edmondson, D.E. and Singer, T.P. 8α-O-Tyrosyl-FAD: a new form of covalently bound flavin from p-cresol methylhydroxylase. J. Biol. Chem. 255 (1980) 6553-6555. [PMID: 7391034]
3. Hopper, D.J., Jones, M.R. and Causer, M.J. Periplasmic location of p-cresol methylhydroxylase in Pseudomonas putida. FEBS Lett. 182 (1985) 485-488. [PMID: 3920077]
4. Bossert, I.D., Whited, G., Gibson, D.T. and Young, L.Y. Anaerobic oxidation of p-cresol mediated by a partially purified methylhydroxylase from a denitrifying bacterium. J. Bacteriol. 171 (1989) 2956-2962. [PMID: 2722739]
5. Reeve, C.D., Carver, M.A. and Hopper, D.J. Stereochemical aspects of the oxidation of 4-ethylphenol by the bacterial enzyme 4-ethylphenol methylenehydroxylase. Biochem. J. 269 (1990) 815-819. [PMID: 1697166]
6. Peters, F., Heintz, D., Johannes, J., van Dorsselaer, A. and Boll, M. Genes, enzymes, and regulation of para-cresol metabolism in Geobacter metallireducens. J. Bacteriol. 189 (2007) 4729-4738. [PMID: 17449613]
7. Johannes, J., Bluschke, A., Jehmlich, N., von Bergen, M. and Boll, M. Purification and characterization of active-site components of the putative p-cresol methylhydroxylase membrane complex from Geobacter metallireducens. J. Bacteriol. 190 (2008) 6493-6500. [PMID: 18658262]
Accepted name: (+)-pinoresinol hydroxylase
Reaction: (+)-pinoresinol + 2 oxidized azurin + H2O = (+)-6-hydroxypinoresinol + 2 reduced azurin + 2 H+
Other name(s): pinoresinol α-hydroxylase; pinAB (gene names)
Systematic name: (+)-pinoresinol:azurin oxidoreductase
Comments: Contains FAD. This enzyme, characterized from the bacterium Pseudomonas sp. SG-MS2, catalyses the incorporation of an oxygen atom originating from a water molecule into position C-6 of the lignan (+)-pinoresinol. The enzyme consists of a flavoprotein subunit and a c-type cytochrome subunit. Electrons that originate in the substrate are transferred via the FAD cofactor and the cytochrome subunit to the blue-copper protein azurin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Shettigar, M., Balotra, S., Kasprzak, A., Pearce, S.L., Lacey, M.J., Taylor, M.C., Liu, J.W., Cahill, D., Oakeshott, J.G. and Pandey, G. Oxidative catabolism of (+)-pinoresinol is initiated by an unusual flavocytochrome encoded by translationally coupled genes within a cluster of (+)-pinoresinol-coinduced genes in Pseudomonas sp. strain SG-MS2. Appl. Environ. Microbiol. 86 (2020) e00375-20. [PMID: 32198167]
Accepted name: bacteriochlorophyllide c C-71-hydroxylase
Reaction: 2 S-adenosyl-L-methionine + a bacteriochlorophyllide c + H2O = a bacteriochlorophyllide e + 2 5'-deoxyadenosine + 2 L-methionine (overall reaction)
(1a) S-adenosyl-L-methionine + a bacteriochlorophyllide c + H2O = a 7-(hydroxymethyl)bacteriochlorophyllide c + 5'-deoxyadenosine + L-methionine
(1b) S-adenosyl-L-methionine + a 7-(hydroxymethyl)bacteriochlorophyllide c + H2O = a 7-(dihydroxymethyl)bacteriochlorophyllide c + 5'-deoxyadenosine + L-methionine
(1c) a 7-(dihydroxymethyl)bacteriochlorophyllide c = a bacteriochlorophyllide e + H2O (spontaneous)
For diagram of reaction click here.
Other name(s): bciD (gene name)
Systematic name: bacteriochlorophyllide-c:S-adenosyl-L-methionine oxidoreductase (C-71-hydroxylating)
Comments: The enzyme, found in green sulfur bacteria (Chlorobiaceae), is a radical S-adenosyl-L-methionine (AdoMet) enzyme and contains a [4Fe-4S] cluster. It catalyses two consecutive hydroxylation reactions of the C-7 methyl group of bacteriochlorophyllide c to form a geminal diol intermediate that spontaneously dehydrates to produce the formyl group of bacteriochlorophyllide e.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Harada, J., Mizoguchi, T., Satoh, S., Tsukatani, Y., Yokono, M., Noguchi, M., Tanaka, A. and Tamiaki, H. Specific gene bciD for C7-methyl oxidation in bacteriochlorophyll e biosynthesis of brown-colored green sulfur bacteria. PLoS One 8 (2013) e60026. [PMID: 23560066]
2. Thweatt, J.L., Ferlez, B.H., Golbeck, J.H. and Bryant, D.A. BciD is a radical S-adenosyl-L-methionine (SAM) enzyme that completes bacteriochlorophyllide e biosynthesis by oxidizing a methyl group into a formyl group at C-7. J. Biol. Chem. 292 (2017) 1361-1373. [PMID: 27994052]
Accepted name: formate dehydrogenase (coenzyme F420)
Reaction: formate + oxidized coenzyme F420 = CO2 + reduced coenzyme F420
Other name(s): coenzyme F420 reducing formate dehydrogenase; coenzyme F420-dependent formate dehydrogenase
Systematic name: formate:coenzyme-F420 oxidoreductase
Comments: The enzyme, characterized from methanogenic archaea, is involved in formate-dependent H2 production. It contains noncovalently bound FAD [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Schauer, N.L. and Ferry, J.G. FAD requirement for the reduction of coenzyme F420 by formate dehydrogenase from Methanobacterium formicicum. J. Bacteriol. 155 (1983) 467-472. [PMID: 6874636]
2. Schauer, N.L. and Ferry, J.G. Composition of the coenzyme F420-dependent formate dehydrogenase from Methanobacterium formicicum. J. Bacteriol. 165 (1986) 405-411. [PMID: 3944055]
3. Lupa, B., Hendrickson, E.L., Leigh, J.A. and Whitman, W.B. Formate-dependent H2 production by the mesophilic methanogen Methanococcus maripaludis. Appl. Environ. Microbiol. 74 (2008) 6584-6590. [PMID: 18791018]
Accepted name: formate dehydrogenase (hydrogenase)
Reaction: formate + an [oxidized hydrogenase] = CO2 + a [reduced hydrogenase]
Other name(s): FDHH; FDH-H; FDH-O; formate dehydrogenase H; formate dehydrogenase O
Systematic name: formate:[oxidized hydrogenase] oxidoreductase
Comments: Formate dehydrogenase H is a cytoplasmic enzyme that oxidizes formate without oxygen transfer, transferring electrons to a hydrogenase. The two enzymes form the formate-hydrogen lyase complex [1]. The enzyme contains an [4Fe-4S] cluster, a selenocysteine residue and a molybdopterin cofactor [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Axley, M.J., Grahame, D.A. and Stadtman, T.C. Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component. J. Biol. Chem. 265 (1990) 18213-18218. [PMID: 2211698]
2. Gladyshev, V.N., Boyington, J.C., Khangulov, S.V., Grahame, D.A., Stadtman, T.C. and Sun, P.D. Characterization of crystalline formate dehydrogenase H from Escherichia coli. Stabilization, EPR spectroscopy, and preliminary crystallographic analysis. J. Biol. Chem. 271 (1996) 8095-8100. [PMID: 8626495]
3. Khangulov, S.V., Gladyshev, V.N., Dismukes, G.C. and Stadtman, T.C. Selenium-containing formate dehydrogenase H from Escherichia coli: a molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer. Biochemistry 37 (1998) 3518-3528. [PMID: 9521673]
Accepted name: ethylbenzene hydroxylase
Reaction: ethylbenzene + H2O + acceptor = (S)-1-phenylethanol + reduced acceptor
For diagram click here.
Other names: ethylbenzene dehydrogenase; ethylbenzene:(acceptor) oxidoreductase
Systematic name: ethylbenzene:acceptor oxidoreductase
Comments: Involved in the anaerobic catabolism of ethylbenzene by denitrifying bacteria. Ethylbenzene is the preferred substrate; the enzyme from some strains oxidizes propylbenzene, 1-ethyl-4-fluorobenzene, 3-methylpent-2-ene and ethylidenecyclohexane. Toluene is not oxidized. p-Benzoquinone or ferrocenium can act as electron acceptor. Contains molybdopterin, [4Fe-4S] clusters and heme b.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 372947-56-3
References:
1. Kniemeyer, O. and Heider, J. Ethylbenzene dehydrogenase, a novel hydrocarbon-oxidising molybdenum/iron-sulfur/heme enzyme. J. Biol. Chem. 276 (2001) 21381-21386. [PMID: 11294876]
2. Johnson, H.A., Pelletier, D.A. and Spormann, A.M. Isolation and characterisation of anaerobic ethylbenzene dehydrogenase, a novel Mo-Fe-S enzyme. J. Bacteriol. 183 (2001) 4536-4542. [PMID: 11443088]
Accepted name: 3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA 24-hydroxylase
Reaction: (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oyl-CoA + H2O + acceptor = (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestan-26-oyl-CoA + reduced acceptor
For diagram click here.
Other name(s): trihydroxycoprostanoyl-CoA oxidase; THC-CoA oxidase; THCA-CoA oxidase; 3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA oxidase; 3α,7α,12α-trihydroxy-5β-cholestan-26-oate 24-hydroxylase
Systematic name: (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oyl-CoA:acceptor 24-oxidoreductase (24R-hydroxylating)
Comments: Requires ATP. The reaction in mammals possibly involves dehydrogenation to give a 24(25)-double bond followed by hydration [1]. However, in amphibians such as the Oriental fire-bellied toad (Bombina orientalis), it is probable that the product is formed via direct hydroxylation of the saturated side chain of (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate and not via hydration of a 24(25) double bond [5]. In microsomes, the free acid is preferred to the coenzyme A ester, whereas in mitochondria, the coenzyme A ester is preferred to the free-acid form of the substrate [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 119799-47-2
References:
1. Gustafsson, J. Biosynthesis of cholic acid in rat liver. 24-Hydroxylation of 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 250 (1975) 8243-8247. [PMID: 240854]
2. Schepers, L., Van Veldhoven, P.P., Casteels, M., Eyssen, H.J. and Mannaerts, G.P. Presence of three acyl-CoA oxidases in rat liver peroxisomes. An inducible fatty acyl-CoA oxidase, a noninducible fatty acyl-CoA oxidase, and a noninducible trihydroxycoprostanoyl-CoA oxidase. J. Biol. Chem. 265 (1990) 5242-5246. [PMID: 2156865]
3. Dieuaide-Noubhani, M., Novikov, D., Baumgart, E., Vanhooren, J.C., Fransen, M., Goethals, M., Vandekerckhove, J., Van Veldhoven, P.P. and Mannaerts, G.P. Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids di- and tri-hydroxycoprostanic acids are metabolized by separate multifunctional proteins. Eur. J. Biochem. 240 (1996) 660-666. [PMID: 8856068]
4. Dieuaide-Noubhani, M., Novikov, D., Baumgart, E., Vanhooren, J.C., Fransen, M., Goethals, M., Vandekerckhove, J., Van Veldhoven, P.P. and Mannaerts, G.P. Erratum report. Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids di- and tri-hydroxycoprostanic acids are metabolized by separate multifunctional proteins. Eur. J. Biochem. 243 (1997) 537. [PMID: 8856068]
5. Pedersen, J.I., Eggertsen, G., Hellman, U., Andersson, U. and Björkhem, I. Molecular cloning and expression of cDNA encoding 3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA oxidase from rabbit liver. J. Biol. Chem. 272 (1997) 18481-18489. [PMID: 9218493]
6. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]
Accepted name: uracil/thymine dehydrogenase
Reaction: (1) uracil + H2O + acceptor = barbiturate + reduced acceptor
(2) thymine + H2O + acceptor = 5-methylbarbiturate + reduced acceptor
For diagram, click here
Other name(s): uracil oxidase; uracil-thymine oxidase; uracil dehydrogenase
Systematic name: uracil:acceptor oxidoreductase
Comments: Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with EC 3.5.2.1 (barbiturase) and EC 3.5.1.95 (N-malonylurea hydrolase). Mammals, plants and other microorganisms utilize the reductive pathway, comprising EC 1.3.1.1 [dihydrouracil dehydrogenase (NAD+)] or EC 1.3.1.2 [dihydropyrimidine dehydrogenase (NADP+)], EC 3.5.2.2 (dihydropyrimidinase) and EC 3.5.1.6 (β-ureidopropionase), with the ultimate degradation products being an L-amino acid, NH3 and CO2 [5].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Hayaishi, O. and Kornberg, A. Metabolism of cytosine, thymine, uracil, and barbituric acid by bacterial enzymes. J. Biol. Chem. 197 (1952) 717-723. [PMID: 12981104]
2. Wang, T.P. and Lampen, J.O. Metabolism of pyrimidines by a soil bacterium. J. Biol. Chem. 194 (1952) 775-783. [PMID: 14927671]
3. Wang, T.P. and Lampen, J.O. Metabolism of pyrimidines by a soil bacterium. J. Biol. Chem. 194 (1952) 775-783. [PMID: 14927671]
4. Lara, F.J.S. On the decomposition of pyrimidines by bacteria. II. Studies with cell-free enzyme preparations. J. Bacteriol. 64 (1952) 279-285. [PMID: 14955523]
5. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme, ureidomalonase. Biochem. Biophys. Res. Commun. 286 (2001) 222-226. [PMID: 11485332]
[EC 1.17.99.5 Transferred entry: bile-acid 7α-dehydroxylase. Now classified as EC 1.17.98.1, bile-acid 7α-dehydroxylase. (EC 1.17.99.5 created 2005 as EC 1.17.1.6, transferred 2006 to EC 1.17.99.5, deleted 2014)]
Accepted name: epoxyqueuosine reductase
Reaction: queuosine34 in tRNA + acceptor + H2O = epoxyqueuosine34 in tRNA + reduced acceptor
For diagram of reaction click here.
Glossary: queuine = base Q = 2-amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-1,7-dihydropyrrolo[3,2-e]pyrimidin-4-one
epoxyqueine = base oQ
Other name(s): oQ reductase; queG (gene name); queH (gene name)
Systematic name: queuosine34 in tRNA:acceptor oxidoreductase
Comments: This enzyme catalyses the last step in the bacterial biosynthetic pathway to queuosine, the modified guanosine base in the wobble position in tRNAs specific for Tyr, His, Asp or Asn. Two types of enzymes are known to catalyse this activity. QueG enzymes are cobalamin-dependent, while QueH enzymes contain a [4Fe-4S] metallocluster along with an adjacent coordinated iron metal.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Miles, Z.D., McCarty, R.M., Molnar, G. and Bandarian, V. Discovery of epoxyqueuosine (oQ) reductase reveals parallels between halorespiration and tRNA modification. Proc. Natl. Acad. Sci. USA 108 (2011) 7368-7372. [PMID: 21502530]
2. Zallot, R., Ross, R., Chen, W.H., Bruner, S.D., Limbach, P.A. and de Crecy-Lagard, V. Identification of a novel epoxyqueuosine reductase family by comparative genomics. ACS Chem. Biol. 12 (2017) 844Ð851. [PMID: 28128549]
3. Li, Q., Zallot, R., MacTavish, B.S., Montoya, A., Payan, D.J., Hu, Y., Gerlt, J.A., Angerhofer, A., de Crecy-Lagard, V. and Bruner, S.D. Epoxyqueuosine reductase QueH in the biosynthetic pathway to tRNA queuosine is a unique metalloenzyme. Biochemistry 60 (2021) 3152-3161. [PMID: 34652139]
[EC 1.17.99.7 Transferred entry: formate dehydrogenase (acceptor). Now classified as EC 1.17.98.4, formate dehydrogenase (hydrogenase). (EC 1.17.99.7 created 2010 as EC 1.1.99.33, transferred 2017 to EC 1.17.99.7, deleted 2020)]
Accepted name: limonene dehydrogenase
Reaction: (1) (S)-limonene + H2O + acceptor = (–)-perillyl alcohol + reduced acceptor
(2) (R)-limonene + H2O + acceptor = (+)-perillyl alcohol + reduced acceptor
Glossary: limonene = 1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
perillyl alcohol = [4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(–)-perillyl alcohol = (S)-perillyl alcohol = [(4S)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(+)-perillyl alcohol = (R)-perillyl alcohol = [(4R)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(–)-limonene = (S)-limonene = (4S)-1-methyl-4-(prop-1-en-2-yl)cyclohexene
(+)-limonene = (R)-limonene = (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohexene
Other name(s): ctmAB (gene names)
Systematic name: limonene:acceptor oxidoreductase (7-hydroxylating)
Comments: Contains FAD. The enzyme, characterized from the bacterium Castellaniella defragrans 65Phen, hydroxylates the R- and S-enantiomers at a similar rate. The in vivo electron acceptor may be a heterodimeric electron transfer flavoprotein (ETF).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Petasch, J., Disch, E.M., Markert, S., Becher, D., Schweder, T., Huttel, B., Reinhardt, R. and Harder, J. The oxygen-independent metabolism of cyclic monoterpenes in Castellaniella defragrans 65Phen. BMC Microbiol. 14 (2014) 164. [PMID: 24952578]
2. Puentes-Cala, E., Liebeke, M., Markert, S. and Harder, J. Limonene dehydrogenase hydroxylates the allylic methyl group of cyclic monoterpenes in the anaerobic terpene degradation by Castellaniella defragrans. J. Biol. Chem. 293 (2018) 9520-9529. [PMID: 29716998]
Accepted name: heme a synthase
Reaction: ferroheme o + H2O + 2 acceptor = ferroheme a + 2 reduced acceptor (overall reaction)
(1a) ferroheme o + H2O + acceptor = ferroheme i + reduced acceptor
(1b) ferroheme i + H2O + acceptor = hydroxyferroheme i + reduced acceptor
(1c) hydroxyferroheme i = ferroheme a + H2O (spontaneous)
Other name(s): COX15 (gene name); ctaA (gene name)
Systematic name: ferroheme o:acceptor C-81-oxidoreductase (heme a-forming)
Comments: Contains a heme b cofactor. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a [2,4]. The electrons produced by the reaction are transferred to a heme b cofactor [6]. However, the electron acceptor that is used to restore the heme b cofactor to its oxidized state is still not known (both a thioredoxin-like protein and menaquinol have been proposed).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Barros, M.H., Carlson, C.G., Glerum, D.M. and Tzagoloff, A. Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O. FEBS Lett. 492 (2001) 133-138. [PMID: 11248251]
2. Brown, K.R., Allan, B.M., Do, P. and Hegg, E.L. Identification of novel hemes generated by heme A synthase: evidence for two successive monooxygenase reactions. Biochemistry 41 (2002) 10906-10913. [PMID: 12206660]
3. Brown, K.R., Brown, B.M., Hoagland, E., Mayne, C.L. and Hegg, E.L. Heme A synthase does not incorporate molecular oxygen into the formyl group of heme A. Biochemistry 43 (2004) 8616-8624. [PMID: 15236569]
4. Hederstedt, L., Lewin, A. and Throne-Holst, M. Heme A synthase enzyme functions dissected by mutagenesis of Bacillus subtilis CtaA. J. Bacteriol. 187 (2005) 8361-8369. [PMID: 16321940]
5. Hederstedt, L. Heme A biosynthesis. Biochim. Biophys. Acta 1817 (2012) 920-927. [PMID: 22484221]
6. Niwa, S., Takeda, K., Kosugi, M., Tsutsumi, E., Mogi, T. and Miki, K. Crystal structure of heme A synthase from Bacillus subtilis. Proc. Natl. Acad. Sci. USA 115 (2018) 11953-11957. [PMID: 30397130]
Accepted name: steroid C-25 hydroxylase
Reaction: cholest-4-en-3-one + acceptor + H2O = 25-hydroxycholest-4-en-3-one + reduced acceptor
For diagram of reaction, click here
Other name(s): s25dA1 (gene name); s25dA1B3 (gene name); s25dA1C3 (gene name); cholesterol C-25 dehydrogenase; steroid C-25 dehydrogenase
Systematic name: cholest-4-en-3-one:acceptor oxidoreductase (25-hydroxylating)
Comments: The enzyme, characterized from the bacterium Sterolibacterium denitrificans, participates in the anaerobic degradation of cholesterol. The enzyme can accept several substrates including vitamin D3. The enzyme contains a bis(guanylyl molybdopterin) cofactor, five [Fe-S] clusters, and one heme b. cf. EC 1.14.99.38, cholesterol 25-monooxygenase, an oxygen-requiring eukaryotic enzyme that catalyses a similar transformation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Dermer, J. and Fuchs, G. Molybdoenzyme that catalyzes the anaerobic hydroxylation of a tertiary carbon atom in the side chain of cholesterol. J. Biol. Chem. 287 (2012) 36905-36916. [PMID: 22942275]
2. Rugor, A., Tataruch, M., Staron, J., Dudzik, A., Niedzialkowska, E., Nowak, P., Hogendorf, A., Michalik-Zym, A., Napruszewska, D.B., Jarzebski, A., Szymanska, K., Bialas, W. and Szaleniec, M. Regioselective hydroxylation of cholecalciferol, cholesterol and other sterol derivatives by steroid C25 dehydrogenase. Appl. Microbiol. Biotechnol. 101 (2017) 1163-1174. [PMID: 27726023]
3. Rugor, A., Wojcik-Augustyn, A., Niedzialkowska, E., Mordalski, S., Staron, J., Bojarski, A. and Szaleniec, M. Reaction mechanism of sterol hydroxylation by steroid C25 dehydrogenase - Homology model, reactivity and isoenzymatic diversity. J. Inorg. Biochem. 173 (2017) 28-43. [PMID: 28482186]
4. Jacoby, C., Eipper, J., Warnke, M., Tiedt, O., Mergelsberg, M., Stark, H.J., Daus, B., Martin-Moldes, Z., Zamarro, M.T., Diaz, E. and Boll, M. Four molybdenum-dependent steroid C-25 hydroxylases: heterologous overproduction, role in steroid degradation, and application for 25-hydroxyvitamin D3 synthesis. mBio 9 (2018) e00694-18. [PMID: 29921665]
Accepted name: 3-oxo-Δ1-steroid hydratase/dehydrogenase
Reaction: a 3-oxo-Δ1-steroid + H2O + acceptor = a steroid 1,3-dione + reduced acceptor (overall reaction)
(1a) a 3-oxo-Δ1-steroid + H2O = a 1-hydroxy-3-oxo-steroid
(1b) a 1-hydroxy-3-oxo-steroid + acceptor = a steroid 1,3-dione + reduced acceptor
Glossary: Δ1-dihydrotestosterone = 17β-hydroxy-5α-androst-1-en-3-one
Other name(s): atcABC (gene names)
Systematic name: 3-oxo-Δ1-steroid:acceptor 1-oxidoreductase
Comments: A molybdenum enzyme. The enzyme, characterized from the bacterium Steroidobacter denitrificans, is involved in the anaetrobic degradation of steroids. It is specific to 3-oxo-Δ1-steroids such as androsta-1-ene-3,17-dione and Δ1-dihydrotestosterone and does not act on 3-oxo-Δ4-steroids.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Yang, F.C., Chen, Y.L., Tang, S.L., Yu, C.P., Wang, P.H., Ismail, W., Wang, C.H., Ding, J.Y., Yang, C.Y., Yang, C.Y. and Chiang, Y.R. Integrated multi-omics analyses reveal the biochemical mechanisms and phylogenetic relevance of anaerobic androgen biodegradation in the environment. ISME J. 10 (2016) 1967-1983. [PMID: 26872041]
EC 1.18.1 With NAD+ or NADP+ as acceptor
EC 1.18.6 With dinitrogen as acceptor
EC 1.18.99 With H+ as acceptor
Accepted name: rubredoxin—NAD+ reductase
Reaction: 2 reduced rubredoxin + NAD+ + H+ = 2 oxidized rubredoxin + NADH
Glossary entries:
rubredoxin = iron-containing protein found in sulfur-metabolizing bacteria and archaea, participating in electron transfer
Other name(s): rubredoxin reductase; rubredoxin-nicotinamide adenine dinucleotide reductase; dihydronicotinamide adenine dinucleotide-rubredoxin reductase; reduced nicotinamide adenine dinucleotide-rubredoxin reductase; NADH-rubredoxin reductase; rubredoxin-NAD reductase; NADH: rubredoxin oxidoreductase; DPNH-rubredoxin reductase; NADH-rubredoxin oxidoreductase
Systematic name: rubredoxin:NAD+ oxidoreductase
Comments: Requires FAD. The enzyme from Clostridium acetobutylicum reduces rubredoxin, ferricyanide and dichlorophenolindophenol, but not ferredoxin or flavodoxin. The reaction does not occur when NADPH is substituted for NADH. Contains iron at the redox centre. Formerly EC 1.6.7.2.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-27-3
References:
1. Peterson, J.A., Kusunose, M., Kusunose, E. and Coon, M.J. Enzymatic ω-oxidation. II. Function of rubredoxin as the electron carrier in ω-hydroxylation. J. Biol. Chem. 242 (1967) 4334-4340. [PMID: 4294330]
2. Ueda, T., Lode, E.T. and Coon, M.J. Enzymatic ω-oxidation. VI. Isolation of homogeneous reduced diphosphopyridine nucleotide-rubredoxin reductase. J. Biol. Chem. 247 (1972) 2109-2116. [PMID: 4335861]
3. Ueda, T., Lode, E.T. and Coon, M.J. Enzymatic oxidation. VII. Reduced diphosphopyridine nucleotide-rubredoxin reductase: properties and function as an electron carrier in hydroxylation. J. Biol. Chem. 247 (1972) 5010-5016. [PMID: 4403503]
4. Petitdemange, H., Marczak, R., Blusson, H. and Gay, R. Isolation and properties of reduced nicotinamide adenine dinucleotide rubredoxin oxidoreductase of Clostridium acetobutylicum. Biochem. Biophys. Res. Commun. 91 (1979) 1258-1265. [PMID: 526302]
Accepted name: ferredoxin—NADP+ reductase
Reaction: 2 reduced ferredoxin + NADP+ + H+ = 2 oxidized ferredoxin + NADPH
For diagram of reaction, click here
Other name(s): ferredoxin-nicotinamide adenine dinucleotide phosphate reductase; ferredoxin-NADP+ reductase; TPNH-ferredoxin reductase; ferredoxin-NADP+ oxidoreductase; NADP+:ferredoxin oxidoreductase; ferredoxin-TPN reductase; ferredoxin-NADP+-oxidoreductase; NADPH:ferredoxin oxidoreductase; ferredoxin-nicotinamide-adenine dinucleotide phosphate (oxidized) reductase
Systematic name: ferredoxin:NADP+ oxidoreductase
Comments: A flavoprotein (FAD). In chloroplasts and cyanobacteria the enzyme acts on plant-type [2Fe-2S] ferredoxins, but in other bacteria it can also reduce bacterial 2[4Fe-4S] ferredoxins and flavodoxin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9029-33-8
References:
1. Shin, M., Tagawa, K. and Arnon, D.I. Crystallization of ferredoxin-TPN reductase and its role in the photosynthetic apparatus of chloroplasts. Biochem. Z. 338 (1963) 84-96.
2. Knaff, D.B. and Hirasawa, M. Ferredoxin-dependent chloroplast enzymes. Biochim. Biophys. Acta 1056 (1991) 93-125. [PMID: 1671559]
3. Karplus, P.A., Daniels, M.J. and Herriott, J.R. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Science 251 (1991) 60-66. [PMID: 1986412]
4. Morales, R., Charon, M.H., Kachalova, G., Serre, L., Medina, M., Gomez-Moreno, C. and Frey, M. A redox-dependent interaction between two electron-transfer partners involved in photosynthesis. EMBO Rep. 1 (2000) 271-276. [PMID: 11256611]
Accepted name: ferredoxin—NAD+ reductase
Reaction: (1) 2 reduced [2Fe-2S] ferredoxin + NAD+ + H+ = 2 oxidized [2Fe-2S] ferredoxin + NADH
(2) reduced 2[4Fe-4S] ferredoxin + NAD+ + H+ = oxidized 2[4Fe-4S] ferredoxin + NADH
Glossary: ferredoxin
Other name(s): ferredoxin-nicotinamide adenine dinucleotide reductase; ferredoxin reductase; NAD+-ferredoxin reductase; NADH-ferredoxin oxidoreductase; reductase, reduced nicotinamide adenine dinucleotide-ferredoxin; ferredoxin-NAD+ reductase; NADH-ferredoxin reductase; NADH2-ferredoxin oxidoreductase; NADH flavodoxin oxidoreductase; NADH-ferredoxinNAP reductase (component of naphthalene dioxygenase multicomponent enzyme system); ferredoxin-linked NAD+ reductase; NADH-ferredoxinTOL reductase (component of toluene dioxygenase); ferredoxin—NAD reductase
Systematic name: ferredoxin:NAD+ oxidoreductase
Comments: Contains FAD. Reaction (1) is written for a [2Fe-2S] ferredoxin, which is characteristic of some mono- and dioxygenase systems. The alternative reaction (2) is written for a 2[4Fe-4S] ferredoxin, which transfers two electrons, and occurs in metabolism of anaerobic bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 39369-37-4
References:
1. Jungerman, K., Thauer, R.F., Leimenstoll, G. and Decker, K. Function of reduced pyridine nucleotide-ferredoxin oxidoreductases in saccharolytic Clostridia. Biochim. Biophys. Acta 305 (1973) 268-280. [PMID: 4147457]
2. Haigler, B.E. and Gibson, D.T. Purification and properties of NADH-ferredoxinNAP reductase, a component of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816. J. Bacteriol. 172 (1990) 457-464. [PMID: 2294092]
3. Ramachandra, M., Seetharam, R., Emptage, M.H. and Sariaslani, F.S. Purification and characterization of a soybean flour-inducible ferredoxin reductase of Streptomyces griseus. J. Bacteriol. 173 (1991) 7106-7112. [PMID: 1938912]
4. Shaw, J.P. and Harayama, S. Purification and characterisation of the NADH:acceptor reductase component of xylene monooxygenase encoded by the TOL plasmid pWW0 of Pseudomonas putida mt-2. Eur. J. Biochem. 209 (1992) 51-61. [PMID: 1327782]
Accepted name: rubredoxin—NAD(P)+ reductase
Reaction: 2 reduced rubredoxin + NAD(P)+ + H+ = 2 oxidized rubredoxin + NAD(P)H
Glossary: benzyl viologen = 1,1'-dibenzyl-4,4'-bipyridinium
2,6-dichloroindophenol = 4-(2,6-dichloro-4-hydroxyphenylimino)cyclohexa-2,5-dien-1-one
menadione = 2-methyl-1,4-naphthoquinone
rubredoxin = iron-containing protein found in sulfur-metabolizing bacteria and archaea, participating in electron transfer
Other name(s): rubredoxin-nicotinamide adenine dinucleotide (phosphate) reductase; rubredoxin-nicotinamide adenine; dinucleotide phosphate reductase; NAD(P)+-rubredoxin oxidoreductase; NAD(P)H-rubredoxin oxidoreductase
Systematic name: rubredoxin:NAD(P)+ oxidoreductase
Comments: The enzyme from Pyrococcus furiosus requires FAD. It reduces a number of electron carriers, including benzyl viologen, menadione and 2,6-dichloroindophenol, but rubredoxin is the most efficient. Ferredoxin is not utilized.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 80237-97-4
References:
1. Petitdemange, H., Blusson, H. and Gay, R. Detection of NAD(P)H-rubredoxin oxidoreductases in Clostridia. Anal. Biochem. 116 (1981) 564-570. [PMID: 6274224]
2. Ma, K. and Adams, M.W.W. A hyperactive NAD(P)H:rubredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus. J. Bacteriol. 181 (1999) 5530-5533. [PMID: 10464233]
Accepted name: putidaredoxin—NAD+ reductase
Reaction: reduced putidaredoxin + NAD+ = oxidized putidaredoxin + NADH + H+
For diagram of reaction click here.
Other name(s): putidaredoxin reductase; camA (gene name)
Systematic name: putidaredoxin:NAD+ oxidoreductase
Comments: Requires FAD. The enzyme from Pseudomonas putida reduces putidaredoxin. It contains a [2Fe-2S] cluster. Involved in the camphor monooxygenase system (see EC 1.14.15.1, camphor 5-monooxygenase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Roome, P.W., Jr., Philley, J.C. and Peterson, J.A. Purification and properties of putidaredoxin reductase. J. Biol. Chem. 258 (1983) 2593-2598. [PMID: 6401738]
2. Koga, H., Yamaguchi, E., Matsunaga, K., Aramaki, H. and Horiuchi, T. Cloning and nucleotide sequences of NADH-putidaredoxin reductase gene (camA) and putidaredoxin gene (camB) involved in cytochrome P-450cam hydroxylase of Pseudomonas putida. J. Biochem. 106 (1989) 831-836. [PMID: 2613690]
3. Peterson, J.A., Lorence, M.C. and Amarneh, B. Putidaredoxin reductase and putidaredoxin. Cloning, sequence determination, and heterologous expression of the proteins. J. Biol. Chem. 265 (1990) 6066-6073. [PMID: 2180940]
4. Sevrioukova, I.F. and Poulos, T.L. Putidaredoxin reductase, a new function for an old protein. J. Biol. Chem. 277 (2002) 25831-25839. [PMID: 12011076]
5. Sevrioukova, I.F., Garcia, C., Li, H., Bhaskar, B. and Poulos, T.L. Crystal structure of putidaredoxin, the [2Fe-2S] component of the P450cam monooxygenase system from Pseudomonas putida. J. Mol. Biol. 333 (2003) 377-392. [PMID: 14529624]
6. Sevrioukova, I.F., Li, H. and Poulos, T.L. Crystal structure of putidaredoxin reductase from Pseudomonas putida, the final structural component of the cytochrome P450cam monooxygenase. J. Mol. Biol. 336 (2004) 889-902. [PMID: 15095867]
7. Smith, N., Mayhew, M., Holden, M.J., Kelly, H., Robinson, H., Heroux, A., Vilker, V.L. and Gallagher, D.T. Structure of C73G putidaredoxin from Pseudomonas putida. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 816-822. [PMID: 15103126]
Accepted name: adrenodoxin-NADP+ reductase
Reaction: 2 reduced adrenodoxin + NADP+ + H+ = 2 oxidized adrenodoxin + NADPH
Other name(s): adrenodoxin reductase; nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase; AdR; NADPH:adrenal ferredoxin oxidoreductase; NADPH-adrenodoxin reductase
Systematic name: reduced adrenodoxin:NADP+ oxidoreductase
Comments: A flavoprotein (FAD). The enzyme, which transfers electrons from NADPH to adrenodoxin molecules, is the first component of the mitochondrial cytochrome P-450 electron transfer systems, and is involved in the biosynthesis of all steroid hormones.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Omura, T., Sanders, E., Estabrook, R.W., Cooper, D.Y. and Rosenthal, O. Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch. Biochem. Biophys. 117 (1966) 660-673.
2. Chu, J.W. and Kimura, T. Studies on adrenal steroid hydroxylases. Molecular and catalytic properties of adrenodoxin reductase (a flavoprotein). J. Biol. Chem. 248 (1973) 2089-2094. [PMID: 4144106]
3. Sugiyama, T. and Yamano, T. Purification and crystallization of NADPH-adrenodoxin reductase from bovine adrenocortical mitochondria. FEBS Lett. 52 (1975) 145-148. [PMID: 235468]
4. Hanukoglu, I. and Jefcoate, C.R. Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin. J. Biol. Chem. 255 (1980) 3057-3061. [PMID: 6766943]
5. Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27-31. [PMID: 3011431]
6. Hanukoglu, I. and Gutfinger, T. cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases. Eur. J. Biochem. 180 (1989) 479-484. [PMID: 2924777]
7. Ziegler, G.A., Vonrhein, C., Hanukoglu, I. and Schulz, G.E. The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis. J. Mol. Biol. 289 (1999) 981-990. [PMID: 10369776]
Accepted name: ferredoxin—NAD(P)+ reductase (naphthalene dioxygenase ferredoxin-specific)
Reaction: 2 reduced [2Fe-2S] ferredoxin + NAD(P)+ + H+ = 2 oxidized [2Fe-2S] ferredoxin + NAD(P)H
Glossary: ferredoxin
Other name(s): NADH-ferredoxin(NAP) reductase
Systematic name: ferredoxin:NAD(P)+ oxidoreductase
Comments: The enzyme from the aerobic bacterium Ralstonia sp. U2 donates electrons to both EC 1.14.12.12, naphthalene 1,2-dioxygenase and EC 1.14.13.172, salicylate 5-hydroxylase [1]. The enzyme from Pseudomonas NCIB 9816 is specific for the ferredoxin associated with naphthalene dioxygenase; it contains FAD and a [2Fe-2S] cluster.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Zhou, N.Y., Al-Dulayymi, J., Baird, M.S. and Williams, P.A. Salicylate 5-hydroxylase from Ralstonia sp. strain U2: a monooxygenase with close relationships to and shared electron transport proteins with naphthalene dioxygenase. J. Bacteriol. 184 (2002) 1547-1555. [PMID: 11872705]
2. Haigler, B.E. and Gibson, D.T. Purification and properties of NADH-ferredoxinNAP reductase, a component of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816. J. Bacteriol. 172 (1990) 457-464. [PMID: 2294092]
[EC 1.18.1.8 Transferred entry: ferredoxin-NAD+ oxidoreductase (Na+-transporting). Now EC 7.2.1.2, ferredoxin—NAD+ oxidoreductase (Na+-transporting) (EC 1.18.1.8 created 2015, deleted 2018)]
[EC 1.18.3.1 Transferred entry: now listed as EC 1.18.99.1 hydrogenase (EC 1.18.3.1 created 1978, deleted 1984)]
Accepted name: nitrogenase
Reaction: 8 reduced ferredoxin + 8 H+ + N2 + 16 ATP + 16 H2O = 8 oxidized ferredoxin + H2 + 2 NH3 + 16 ADP + 16 phosphate
For diagram of reaction click here.
Other name(s): reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing)
Systematic name: ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, molybdenum-dependent)
Comments: Requires Mg2+. The enzyme is a complex of two components (namely dinitrogen reductase and dinitrogenase). Dinitrogen reductase is a [4Fe-4S] protein, which, in the presence of two molecules of ATP, transfers an electron from ferredoxin to the dinitrogenase component. Dinitrogenase is a molybdenum-iron protein that reduces dinitrogen to two molecules of ammonia in three successive two-electron reductions via diazene and hydrazine. The reduction is initiated by formation of hydrogen in stoichiometric amounts [2]. Acetylene is reduced to ethylene (but only very slowly to ethane), azide to nitrogen and ammonia, and cyanide to methane and ammonia. In the absence of a suitable substrate, hydrogen is slowly formed. Ferredoxin may be replaced by flavodoxin [see EC 1.19.6.1 nitrogenase (flavodoxin)]. The enzyme does not reduce CO (cf. EC 1.18.6.2, vanadium-dependent nitrogenase).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9013-04-1
References:
1. Zumft, W.G., Paneque, A., Aparicio, P.J. and Losada, M. Mechanism of nitrate reduction in Chlorella. Biochem. Biophys. Res. Commun. 36 (1969) 980-986. [PMID: 4390523]
2. Liang, J. and Burris, R.H. Hydrogen burst associated with nitrogenase-catalyzed reactions. Proc. Natl. Acad. Sci. USA 85 (1988) 9446-9450. [PMID: 3200830]
3. Dance, I. The mechanism of nitrogenase. Computed details of the site and geometry of binding of alkyne and alkene substrates and intermediates. J. Am. Chem. Soc. 126 (2004) 11852-11863. [PMID: 15382920]
4. Chan, J.M., Wu, W., Dean, D.R. and Seefeldt, L.C. Construction and characterization of a heterodimeric iron protein: defining roles for adenosine triphosphate in nitrogenase catalysis. Biochemistry 39 (2000) 7221-7228. [PMID: 10852721]
Accepted name: vanadium-dependent nitrogenase
Reaction: 12 reduced ferredoxin + 12 H+ + N2 + 40 ATP + 40 H2O = 12 oxidized ferredoxin + 3 H2 + 2 NH3 + 40 ADP + 40 phosphate
Other name(s): vnfD (gene name); vnfG (gene name); vnfK (gene name)
Systematic name: ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, vanadium-dependent)
Comments: Requires Mg2+. This enzyme, originally isolated from the bacterium Azotobacter vinelandii, is a complex of two components (namely dinitrogen reductase and dinitrogenase). Dinitrogen reductase is a [4Fe-4S] protein, which, in the presence of ATP, transfers an electron from ferredoxin to the dinitrogenase component. Dinitrogenase is a vanadium-iron protein that reduces dinitrogen to two molecules of ammonia in three successive two-electron reductions via diazine and hydrazine. Compared with molybdenum-depedent nitrogenase (EC 1.18.6.1), this enzyme produces more dihydrogen and consumes more ATP per dinitrogen molecule being reduced. Unlike EC 1.18.6.1, this enzyme can also use CO as substrate, producing ethene, ethane and propane [7,9].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Eady, R.R., Richardson, T.H., Miller, R.W., Hawkins, M. and Lowe, D.J. The vanadium nitrogenase of Azotobacter chroococcum. Purification and properties of the Fe protein. Biochem. J. 256 (1988) 189-196. [PMID: 2851977]
2. Miller, R.W. and Eady, R.R. Molybdenum and vanadium nitrogenases of Azotobacter chroococcum. Low temperature favours N2 reduction by vanadium nitrogenase. Biochem. J. 256 (1988) 429-432. [PMID: 3223922]
3. Thorneley, R.N., Bergstrom, N.H., Eady, R.R. and Lowe, D.J. Vanadium nitrogenase of Azotobacter chroococcum. MgATP-dependent electron transfer within the protein complex. Biochem. J. 257 (1989) 789-794. [PMID: 2784670]
4. Dilworth, M.J., Eldridge, M.E. and Eady, R.R. Correction for creatine interference with the direct indophenol measurement of NH3 in steady-state nitrogenase assays. Anal. Biochem. 207 (1992) 6-10. [PMID: 1336937]
5. Dilworth, M.J., Eldridge, M.E. and Eady, R.R. The molybdenum and vanadium nitrogenases of Azotobacter chroococcum: effect of elevated temperature on N2 reduction. Biochem. J. 289 (1993) 395-400. [PMID: 8424785]
6. Eady, R.R. Current status of structure function relationships of vanadium nitrogenase. Coordinat. Chem. Rev. 237 (2003) 23-30.
7. Lee, C.C., Hu, Y. and Ribbe, M.W. Vanadium nitrogenase reduces CO. Science 329 (2010) 642. [PMID: 20689010]
8. Lee, C.C., Hu, Y. and Ribbe, M.W. Tracing the hydrogen source of hydrocarbons formed by vanadium nitrogenase. Angew Chem Int Ed Engl 50 (2011) 5545-5547. [PMID: 21538750]
9. Sippel, D. and Einsle, O. The structure of vanadium nitrogenase reveals an unusual bridging ligand. Nat. Chem. Biol. 13 (2017) 956-960. [PMID: 28692069]
[EC 1.18.96.1 Transferred entry: now EC 1.15.1.2, superoxide reductase (EC 1.18.96.1 created 2001, deleted 2001)]
[EC 1.18.99.1 Transferred entry: now EC 1.12.7.2, ferredoxin hydrogenase (EC 1.18.99.1 created 1961 as EC 1.98.1.1, transferred 1965 to EC 1.12.1.1, transferred 1972 to EC 1.12.7.1, transferred 1978 to EC 1.18.3.1, transferred 1984 to EC 1.18.99.1, deleted 2002)]
Accepted name: flavodoxin—NADP+ reductase
Reaction: reduced flavodoxin + NADP+ = oxidized flavodoxin + NADPH + H+
Other name(s): FPR
Systematic name: flavodoxin:NADP+ oxidoreductase
Comments: A flavoprotein (FAD). This activity occurs in some prokaryotes and algae that possess flavodoxin, and provides low-potential electrons for a variety of reactions such as nitrogen fixation, sulfur assimilation and amino acid biosynthesis. In photosynthetic organisms it is involved in the photosynthetic electron transport chain. The enzyme also catalyses EC 1.18.1.2, ferredoxin—NADP+ reductase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. McIver, L., Leadbeater, C., Campopiano, D.J., Baxter, R.L., Daff, S.N., Chapman, S.K. and Munro, A.W. Characterisation of flavodoxin NADP+ oxidoreductase and flavodoxin; key components of electron transfer in Escherichia coli. Eur. J. Biochem. 257 (1998) 577-585. [PMID: 9839946]
2. Leadbeater, C., McIver, L., Campopiano, D.J., Webster, S.P., Baxter, R.L., Kelly, S.M., Price, N.C., Lysek, D.A., Noble, M.A., Chapman, S.K. and Munro, A.W. Probing the NADPH-binding site of Escherichia coli flavodoxin oxidoreductase. Biochem. J. 352 (2000) 257-266. [PMID: 11085917]
3. Wan, J.T. and Jarrett, J.T. Electron acceptor specificity of ferredoxin (flavodoxin):NADP+ oxidoreductase from Escherichia coli. Arch. Biochem. Biophys. 406 (2002) 116-126. [PMID: 12234497]
4. Bortolotti, A., Perez-Dorado, I., Goni, G., Medina, M., Hermoso, J.A., Carrillo, N. and Cortez, N. Coenzyme binding and hydride transfer in Rhodobacter capsulatus ferredoxin/flavodoxin NADP(H) oxidoreductase. Biochim. Biophys. Acta 1794 (2009) 199-210. [PMID: 18973834]
5. Bortolotti, A., Sanchez-Azqueta, A., Maya, C.M., Velazquez-Campoy, A., Hermoso, J.A., Medina, M. and Cortez, N. The C-terminal extension of bacterial flavodoxin-reductases: involvement in the hydride transfer mechanism from the coenzyme. Biochim. Biophys. Acta 1837 (2014) 33-43. [PMID: 24016470]
6. Skramo, S., Hersleth, H.P., Hammerstad, M., Andersson, K.K. and Rohr, A.K. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of a ferredoxin/flavodoxin-NADP(H) oxidoreductase (Bc0385) from Bacillus cereus. Acta Crystallogr. F Struct. Biol. Commun. 70 (2014) 777-780. [PMID: 24915092]
EC 1.19.6 With dinitrogen as acceptor
Accepted name: nitrogenase (flavodoxin)
Reaction: 4 reduced flavodoxin + N2 + 16 ATP + 16 H2O = 4 oxidized flavodoxin + H2 + 2 NH3 + 16 ADP + 16 phosphate
Systematic name: reduced flavodoxin:dinitrogen oxidoreductase (ATP-hydrolysing)
Comments: Requires Mg2+. It is composed of two components, dinitrogen reductase and dinitrogenase, that can be separated but are both required for nitrogenase activity. Dinitrogen reductase is a [4Fe-4S] protein, which, at the expense of ATP, transfers electrons from a dedicated flavodoxin to dinitrogenase. Dinitrogenase is a protein complex that contains either a molybdenum-iron cofactor, a vanadium-iron cofactor, or an iron-iron cofactor, that reduces dinitrogen in three succesive two-electron reductions from nitrogen to diimine to hydrazine to two molecules of ammonia. The reduction is initiated by formation of hydrogen. The enzyme can also reduce acetylene to ethylene (but only very slowly to ethane), azide to nitrogen and ammonia, and cyanide to methane and ammonia. In the absence of a suitable substrate, hydrogen is slowly formed. Some enzymes utilize ferredoxin rather than flavodoxin as the electron donor (see EC 1.18.6.1, nitrogenase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9013-04-1
References:
1. Zumft, W.G. and Mortenson, L.E. The nitrogen-fixing complex of bacteria. Biochim. Biophys. Acta 416 (1975) 1-52. [PMID: 164247]
2. Eady, R.R., Smith, B.E., Cook, K.A. and Postgate, J.R. Nitrogenase of Klebsiella pneumoniae. Purification and properties of the component proteins. Biochem. J. 128 (1972) 655-675. [PMID: 4344006]
3. Deistung, J., Cannon, F.C., Cannon, M.C., Hill, S. and Thorneley, R.N. Electron transfer to nitrogenase in Klebsiella pneumoniae. nifF gene cloned and the gene product, a flavodoxin, purified. Biochem. J. 231 (1985) 743-753. [PMID: 3907625]
EC 1.20.1 With NAD(P)+ as acceptor
EC 1.20.2 With a cytochrome as acceptor
EC 1.20.4 With disulfide as acceptor
EC 1.20.9 With a copper protein as acceptor
EC 1.20.98 With other, known, physiological acceptors
EC 1.20.99 With unknown physiological acceptors
EC 1.20.1 With NAD(P)+ as acceptor
Accepted name: phosphonate dehydrogenase
Reaction: phosphonate + NAD+ + H2O = phosphate + NADH + H+
Other name(s): NAD:phosphite oxidoreductase; phosphite dehydrogenase
Systematic name: phosphonate:NAD+ oxidoreductase
Comments: NADP+ is a poor substitute for NAD+ in the enzyme from Pseudomonas stutzeri WM88.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9031-35-0
References:
1. Costas, A.M.G., White, A.K. and Metcalf, W.W. Purification and characterization of a novel phosphorus-oxidizing enzyme from Pseudomonas stutzeri WM88. J. Biol. Chem. 276 (2001) 17429-17436. [PMID: 11278981]
2. Vrtis, J.M., White, A.K., Metcalf, W.W. and van der Donk, W.A. Phosphite dehydrogenase: An unusual phosphoryl transfer reaction. J. Am. Chem. Soc. 123 (2001) 2672-2673. [PMID: 11456941]
EC 1.20.2.1
Accepted name: arsenate reductase (cytochrome c)
Reaction: arsenite + H2O + 2 oxidized cytochrome c = arsenate + 2 reduced cytochrome c + 2 H+
Other name(s): arsenite oxidase (ambiguous)
Systematic name: arsenite:cytochrome c oxidoreductase
Comments: A molybdoprotein containing iron-sulfur clusters. Isolated from α-proteobacteria. Unlike EC 1.20.9.1, arsenate reductase (azurin), it does not use azurin as acceptor.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
Metacyc,
CAS registry number:
References:
1. vanden Hoven, R.N. and Santini, J.M. Arsenite oxidation by the heterotroph Hydrogenophaga sp. str. NT-14: the arsenite oxidase and its physiological electron acceptor. Biochim. Biophys. Acta 1656 (2004) 148-155. [PMID: 15178476]
2. Santini, J.M., Kappler, U., Ward, S.A., Honeychurch, M.J., vanden Hoven, R.N. and Bernhardt, P.V. The NT-26 cytochrome c552 and its role in arsenite oxidation. Biochim. Biophys. Acta 1767 (2007) 189-196. [PMID: 17306216]
3. Branco, R., Francisco, R., Chung, A.P. and Morais, P.V. Identification of an aox system that requires cytochrome c in the highly arsenic-resistant bacterium Ochrobactrum tritici SCII24. Appl. Environ. Microbiol. 75 (2009) 5141-5147. [PMID: 19525272]
4. Lieutaud, A., van Lis, R., Duval, S., Capowiez, L., Muller, D., Lebrun, R., Lignon, S., Fardeau, M.L., Lett, M.C., Nitschke, W. and Schoepp-Cothenet, B. Arsenite oxidase from Ralstonia sp. 22: characterization of the enzyme and its interaction with soluble cytochromes. J. Biol. Chem. 285 (2010) 20433-20441. [PMID: 20421652]
EC 1.20.4 With disulfide as acceptor
EC 1.20.4.3 mycoredoxin
EC 1.20.4.4 arsenate reductase (thioredoxin)
Accepted name: arsenate reductase (glutathione/glutaredoxin)
Reaction: arsenate + glutathione + glutaredoxin = arsenite + a glutaredoxin-glutathione disulfide + H2O
For diagram of reaction click here
Other name(s): ArsC (ambiguous); arsenate:glutaredoxin oxidoreductase; arsenate reductase (glutaredoxin)
Systematic name: arsenate:glutathione/glutaredoxin oxidoreductase
Comments: The enzyme is part of a system for detoxifying arsenate. The substrate binds to a catalytic cysteine residue, forming a covalent thiolate—As(V) intermediate. A tertiary intermediate is then formed between the arsenic, the enzyme's cysteine, and a glutathione cysteine. This intermediate is reduced by glutaredoxin, which forms a dithiol with the glutathione, leading to the dissociation of arsenite. Thus reduction of As(V) is mediated by three cysteine residues: one in ArsC, one in glutathione, and one in glutaredoxin. Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 7.3.2.7, arsenite-transporting ATPase; in other organisms, arsenite can be methylated by EC 2.1.1.137, arsenite methyltransferase, in a pathway that produces non-toxic organoarsenical compounds. cf. EC 1.20.4.4, arsenate reductase (thioredoxin).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 146907-46-2
References:
1. Gladysheva, T., Liu, J.Y. and Rosen, B.P. His-8 lowers the pKa of the essential Cys-12 residue of the ArsC arsenate reductase of plasmid R773. J. Biol. Chem. 271 (1996) 33256-33260. [PMID: 8969183]
2. Gladysheva, T.B., Oden, K.L. and Rosen, B.P. Properties of the arsenate reductase of plasmid R773. Biochemistry 33 (1994) 7288-7293. [PMID: 8003492]
3. Holmgren, A. and Aslund, F. Glutaredoxin. Methods Enzymol. 252 (1995) 283-292. [PMID: 7476363]
4. Krafft, T. and Macy, J.M. Purification and characterization of the respiratory arsenate reductase of Chrysiogenes arsenatis. Eur. J. Biochem. 255 (1998) 647-653. [PMID: 9738904]
5. Martin, J.L. Thioredoxin - a fold for all reasons. Structure 3 (1995) 245-250. [PMID: 7788290]
6. Radabaugh, T.R. and Aposhian, H.V. Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem. Res. Toxicol. 13 (2000) 26-30. [PMID: 10649963]
7. Sato, T. and Kobayashi, Y. The ars operon in the skin element of Bacillus subtilis confers resistance to arsenate and arsenite. J. Bacteriol. 180 (1998) 1655-1661. [PMID: 9537360]
8. Shi, J., Vlamis-Gardikas, V., Aslund, F., Holmgren, A. and Rosen, B.P. Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli shows that glutaredoxin 2 is the primary hydrogen donor to ArsC-catalyzed arsenate reduction. J. Biol. Chem. 274 (1999) 36039-36042. [PMID: 10593884]
9. Mukhopadhyay, R. and Rosen, B.P. Arsenate reductases in prokaryotes and eukaryotes. Environ Health Perspect 110 Suppl 5 (2002) 745-748. [PMID: 12426124]
10. Messens, J. and Silver, S. Arsenate reduction: thiol cascade chemistry with convergent evolution. J. Mol. Biol. 362 (2006) 1-17. [PMID: 16905151]
Accepted name: methylarsonate reductase
Reaction: methylarsonate + 2 glutathione = methylarsonite + glutathione disulfide + H2O
For diagram click here.
Glossary: methylarsonite = methylarsonous acid
cacodylic acid = dimethylarsinic acid
Other name(s): MMA(V) reductase; gluthathione:methylarsonate oxidoreductase
Systematic name: methylarsonate:glutathione oxidoreductase
Comments: The product, Me-As(OH)2 (methylarsonous acid), is biologically methylated by EC 2.1.1.137, arsenite methyltransferase, to form cacodylic acid (dimethylarsinic acid).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 254889-62-8
References:
1. Zakharyan, R.A. and Aposhian, H.V. Enzymatic reduction of arsenic compounds in mammalian systems: the rate-limiting enzyme of rabbit liver arsenic biotransformation is MMA(V) reductase. Chem. Res. Toxicol. 12 (1999) 1278-1283. [PMID: 10604879]
Accepted name: mycoredoxin
Reaction: arseno-mycothiol + mycoredoxin = arsenite + mycothiol-mycoredoxin disulfide
Glossary: mycothiol = 1-O-[2-(N2-acetyl-L-cysteinamido)-2-deoxy-α-D-glucopyranosyl]-1D-myo-inositol
Other name(s): Mrx1; MrxI
Systematic name: arseno-mycothiol:mycoredoxin oxidoreductase
Comments: Reduction of arsenate is part of a defense mechanism of the cell against toxic arsenate. The substrate arseno-mycothiol is formed by EC 2.8.4.2 (arsenate:mycothiol transferase). A second mycothiol recycles mycoredoxin and forms mycothione.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Ordonez, E., Van Belle, K., Roos, G., De Galan, S., Letek, M., Gil, J.A., Wyns, L., Mateos, L.M. and Messens, J. Arsenate reductase, mycothiol, and mycoredoxin concert thiol/disulfide exchange. J. Biol. Chem. 284 (2009) 15107-15116. [PMID: 19286650]
Accepted name: arsenate reductase (thioredoxin)
Reaction: arsenate + thioredoxin = arsenite + thioredoxin disulfide + H2O
For diagram of reaction click here
Other name(s): ArsC (ambiguous)
Systematic name: arsenate:thioredoxin oxidoreductase
Comments: The enzyme, characterized in bacteria of the Firmicutes phylum, is specific for thioredoxin [1]. It has no activity with glutaredoxin [cf. EC 1.20.4.1, arsenate reductase (glutaredoxin)]. Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 7.3.2.7, arsenite-transporting ATPase; in other organisms, arsenite can be methylated by EC 2.1.1.137, arsenite methyltransferase, in a pathway that produces non-toxic organoarsenical compounds. The enzyme also has the activity of EC 3.1.3.48, protein-tyrosine-phosphatase [3].
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Ji, G., Garber, E.A., Armes, L.G., Chen, C.M., Fuchs, J.A. and Silver, S. Arsenate reductase of Staphylococcus aureus plasmid pI258. Biochemistry 33 (1994) 7294-7299. [PMID: 8003493]
2. Messens, J., Hayburn, G., Desmyter, A., Laus, G. and Wyns, L. The essential catalytic redox couple in arsenate reductase from Staphylococcus aureus. Biochemistry 38 (1999) 16857-16865. [PMID: 10606519]
3. Zegers, I., Martins, J.C., Willem, R., Wyns, L. and Messens, J. Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty. Nat. Struct. Biol. 8 (2001) 843-847. [PMID: 11573087]
4. Messens, J., Martins, J.C., Van Belle, K., Brosens, E., Desmyter, A., De Gieter, M., Wieruszeski, J.M., Willem, R., Wyns, L. and Zegers, I. All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade. Proc. Natl. Acad. Sci. USA 99 (2002) 8506-8511. [PMID: 12072565]
EC 1.20.9.1
Accepted name: arsenate reductase (azurin)
Reaction: arsenite + H2O + 2 oxidized azurin = arsenate + 2 reduced azurin + 2 H+
For diagram of reaction click here
Glossary: Azurin is a blue copper protein found in many bacteria, which undergoes oxidation-reduction between Cu(I) and Cu(II), and transfers single electrons between enzymes.
Other name(s): arsenite oxidase (ambiguous)
Systematic name: arsenite:azurin oxidoreductase
Comments: Contains a molybdopterin centre comprising two molybdopterin guanosine dinucleotide cofactors bound to molybdenum, a [3Fe-4S] cluster and a Rieske-type [2Fe-2S] cluster. Isolated from β-proteobacteria. Also uses a c-type cytochrome or O2 as acceptors.
Links to other databases:
BRENDA,
EAWAG-BBD,
EXPASY,
KEGG,
Metacyc,
PDB,
CAS registry number:
References:
1. Anderson, G.L., Williams, J. and Hille, R. The purification and characterization of arsenite oxidase from Alcaligenes faecalis, a molybdenum-containing hydroxylase. J. Biol. Chem. 267 (1992) 23674-23682. [PMID: 1331097]
2. Ellis, P.J., Conrads, T., Hille, R. and Kuhn, P. Crystal structure of the 100 kDa arsenite oxidase from Alcaligenes faecalis in two crystal forms at 1.64 Å and 2.03 Å. Structure 9 (2001) 125-132. [PMID: 11250197]
EC 1.20.98 With other, known acceptors
[EC 1.20.98.1 Transferred entry: arsenate reductase (azurin). Now EC 1.20.9.1, arsenate reductase (azurin) (EC 1.20.98.1 created 2001, deleted 2011)]
Accepted name: arsenate reductase (donor)
Reaction: arsenite + acceptor = arsenate + reduced acceptor
For diagram of reaction click here.
Other name(s): arsenate:(acceptor) oxidoreductase
Systematic name: arsenate:acceptor oxidoreductase
Comments: Benzyl viologen can act as an acceptor. Unlike EC 1.20.4.1, arsenate reductase (glutaredoxin), reduced glutaredoxin cannot serve as a reductant.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 146907-46-2
References:
1. Krafft, T. and Macy, J.M. Purification and characterization of the respiratory arsenate reductase of Chrysiogenes arsenatis. Eur. J. Biochem. 255 (1998) 647-653. [PMID: 9738904]
2. Radabaugh, T.R. and Aposhian, H.V. Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem. Res. Toxicol. 13 (2000) 26-30. [PMID: 10649963]
EC 1.21.1 With NAD+ or NADP+ as acceptor
EC 1.21.3 With oxygen as acceptor
EC 1.21.99 With other acceptors
Accepted name: iodotyrosine deiodinase
Reaction: L-tyrosine + 2 NADP+ + 2 iodide = 3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+ (overall reaction)
(1a) L-tyrosine + NADP+ + iodide = 3-iodo-L-tyrosine + NADPH + H+
(1b) 3-iodo-L-tyrosine + NADP+ + iodide = 3,5-diiodo-L-tyrosine + NADPH + H+
Other name(s): iodotyrosine dehalogenase 1; DEHAL1
Systematic name: L-tyrosine,iodide:NADP+ oxidoreductase (iodinating)
Comments: The enzyme activity has only been demonstrated in the direction of 3-deiodination. Present in a transmembrane flavoprotein. Requires FMN.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Rosenberg, I.N. Purification of iodotyrosine deiodinase from bovine thyroid. Metabolism 19 (1970) 785-798. [PMID: 4394169]
2. Gnidehou, S., Caillou, B., Talbot, M., Ohayon, R., Kaniewski, J., Noel-Hudson, M.S., Morand, S., Agnangji, D., Sezan, A., Courtin, F., Virion, A. and Dupuy, C. Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site. FASEB J. 18 (2004) 1574-1576. [PMID: 15289438]
3. Friedman, J.E., Watson, J.A., Jr., Lam, D.W. and Rokita, S.E. Iodotyrosine deiodinase is the first mammalian member of the NADH oxidase/flavin reductase superfamily. J. Biol. Chem. 281 (2006) 2812-2819. [PMID: 16316988]
4. Thomas, S.R., McTamney, P.M., Adler, J.M., Laronde-Leblanc, N. and Rokita, S.E. Crystal structure of iodotyrosine deiodinase, a novel flavoprotein responsible for iodide salvage in thyroid glands. J. Biol. Chem. 284 (2009) 19659-19667. [PMID: 19436071]
EC 1.21.1.2
Accepted name: 2,4-dichlorobenzoyl-CoA reductase
Reaction: 4-chlorobenzoyl-CoA + NADP+ + chloride = 2,4-dichlorobenzoyl-CoA + NADPH + H+
Systematic name: 4-chlorobenzoyl-CoA:NADP+ oxidoreductase (halogenating)
Comments: The enzyme, characterized from Corynebacterium strains able to grow on 2,4-dichlorobenzoate, forms part of the 2,4-dichlorobenzoate degradation pathway.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Romanov, V. and Hausinger, R.P. NADPH-dependent reductive ortho dehalogenation of 2,4-dichlorobenzoic acid in Corynebacterium sepedonicum KZ-4 and Coryneform bacterium strain NTB-1 via 2,4-dichlorobenzoyl coenzyme A. J. Bacteriol. 178 (1996) 2656-2661. [PMID: 8626335]
EC 1.21.3 With oxygen as acceptor
Accepted name: isopenicillin-N synthase
Reaction: N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine + O2 = isopenicillin N + 2 H2O
For diagram click here and possible mechanism click here.
Other name(s): isopenicillin N synthetase
Systematic name: N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine:oxygen oxidoreductase (cyclizing)
Comments: Forms part of the penicillin biosynthesis pathway (for pathway, click here).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 78642-31-6
References:
1. Huffman, G.W., Gesellchen, P.D., Turner, J.R., Rothenberger, R.B., Osborne, H.E., Miller, F.D., Chapman, J.L. and Queener, S.W. Substrate specificity of isopenicillin N synthase. J. Med. Chem. 35 (1992) 1897-1914. [PMID: 1588566]
2. Roach, P.L., Clifton, I.J., Fulop, V., Harlos, K., Barton, G.J., Hajdu, J., Andersson, I., Schofield, C.J. and Baldwin, J.E. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature 375 (1995) 700-704. [PMID: 7791906]
Accepted name: columbamine oxidase
Reaction: 2 columbamine + O2 = 2 berberine + 2 H2O
For diagram click here.
Other name(s): berberine synthase
Systematic name: columbamine:oxygen oxidoreductase (cyclizing)
Comments: An iron protein. Oxidation of the O-methoxyphenol structure forms the methylenedioxy group of berberine.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 95329-18-3
References:
1. Rueffer, M. and Zenk, M.H. Berberine synthesis, the methylenedioxy group forming enzyme in berberine synthesis. Tetrahedron Lett. 26 (1985) 201-202.
Accepted name: reticuline oxidase
Reaction: (S)-reticuline + O2 = (S)-scoulerine + H2O2
For diagram click here.
Other name(s): BBE; berberine bridge enzyme; berberine-bridge-forming enzyme; tetrahydroprotoberberine synthase
Systematic name: (S)-reticuline:oxygen oxidoreductase (methylene-bridge-forming)
Comments: Contains FAD. The enzyme from the plant Eschscholtzia californica binds the cofactor covalently [3]. Acts on (S)-reticuline and related compounds, converting the N-methyl group into the methylene bridge ('berberine bridge') of (S)-tetrahydroprotoberberines. The product of the reaction, (S)-scoulerine, is a precursor of protopine, protoberberine and benzophenanthridine alkaloid biosynthesis in plants.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 152232-28-5
References:
1. Steffens, P., Nagakura, N. and Zenk, M.H. The berberine bridge forming enzyme in tetrahydroprotoberberine biosynthesis. Tetrahedron Lett. 25 (1984) 951-952.
2. Dittrich, H. and Kutchan, T.M. Molecular cloning, expression and induction of the berberine bridge enzyme, an enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack. Proc. Natl. Acad. Sci. USA 88 (1991) 9969-9973. [PMID: 1946465]
3. Kutchan, T.M. and Dittrich, H. Characterization and mechanism of the berberine bridge enzyme, a covalently flavinylated oxidase of benzophenanthridine alkaloid biosynthesis in higher plants. J. Biol. Chem. 270 (1995) 24475-24481. [PMID: 7592663]
Accepted name: sulochrin oxidase [(+)-bisdechlorogeodin-forming]
Reaction: 2 sulochrin + O2 = 2 (+)-bisdechlorogeodin + 2 H2O
For diagram click here.
Other name(s): sulochrin oxidase
Systematic name: sulochrin:oxygen oxidoreductase (cyclizing, (+)-specific)
Comments: Also acts on several diphenols and phenylenediamines, but has low affinity for these substrates. Involved in the biosynthesis of mould metabolites related to the antibiotic griseofulvin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 82469-87-2
References:
1. Nordlöv, H. and Gatenbeck, S. Enzymatic synthesis of (+)- and (–)-bisdechlorogeodin with sulochrin oxidase from Penicillium frequentans and Oospora sulphurea ochracea. Arch. Microbiol. 131 (1982) 208-211. [PMID: 7049104]
Accepted name: sulochrin oxidase [(–)-bisdechlorogeodin-forming]
Reaction: 2 sulochrin + O2 = 2 (–)-bisdechlorogeodin + 2 H2O
For diagram click here.
Other name(s): sulochrin oxidase
Systematic name: sulochrin:oxygen oxidoreductase (cyclizing, (–)-specific)
Comments: Also acts on several diphenols and phenylenediamines, but has low affinity for these substrates. Involved in the biosynthesis of mould metabolites related to the antibiotic griseofulvin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 82469-87-2
References:
1. Nordlöv, H. and Gatenbeck, S. Enzymatic synthesis of (+)- and (–)-bisdechlorogeodin with sulochrin oxidase from Penicillium frequentans and Oospora sulphurea ochracea. Arch. Microbiol. 131 (1982) 208-211. [PMID: 7049104]
Accepted name: aureusidin synthase
Reaction: (1) 2',4,4',6'-tetrahydroxychalcone 4'-O-β-D-glucoside + O2 = aureusidin 6-O-β-D-glucoside + H2O
(2) 2',3,4,4',6'-pentahydroxychalcone 4'-O-β-D-glucoside + ½ O2 = aureusidin 6-O-β-D-glucoside + H2O
(3) 2',3,4,4',6'-pentahydroxychalcone 4'-O-β-D-glucoside + O2 = bracteatin 6-O-β-D-glucoside + H2O
For diagram of reaction click here.
Glossary: 2',4,4',6'-tetrahydroxychalcone = 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)prop-2-en-1-one
aureusidin = 4,6-dihydroxy-2-[(3,4-dihydroxyphenyl)methylidene]benzofuran-3(2H)-one
bracteatin = 4,6-dihydroxy-2-[(3,4,5-trihydroxyphenyl)methylidene]benzofuran-3(2H)-one
Other name(s): AmAS1
Systematic name: 2',4,4',6'-tetrahydroxychalcone 4'-O-β-D-glucoside:oxygen oxidoreductase
Comments: A copper-containing glycoprotein that plays a key role in the yellow coloration of flowers such as Antirrhinum majus (snapdragon). The enzyme is a homologue of plant polyphenol oxidase [1] and catalyses two separate chemical transformations, i.e. 3-hydroxylation and oxidative cyclization (2',-dehydrogenation). H2O2 activates reaction (1) but inhibits reaction (2). Originally considered to act on the phenol but now thought to act mainly on the 4'-O-β-D-glucoside in vivo [4].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 320784-48-3
References:
1. Nakayama, T., Yonekura-Sakakibara, K., Sato, T., Kikuchi, S., Fukui, Y., Fukuchi-Mizutani, M., Ueda, T., Nakao, M., Tanaka, Y., Kusumi, T. and Nishino, T. Aureusidin synthase: A polyphenol oxidase homolog responsible for flower coloration. Science 290 (2000) 1163-1166. [PMID: 11073455]
2. Nakayama, T., Sato, T., Fukui, Y., Yonekura-Sakakibara, K., Hayashi, H., Tanaka, Y., Kusumi, T. and Nishino, T. Specificity analysis and mechanism of aurone synthesis catalyzed by aureusidin synthase, a polyphenol oxidase homolog responsible for flower coloration. FEBS Lett. 499 (2001) 107-111. [PMID: 11418122]
3. Sato, T., Nakayama, T., Kikuchi, S., Fukui, Y., Yonekura-Sakakibara, K., Ueda, T., Nishino, T., Tanaka, Y. and Kusumi, T. Enzymatic formation of aurones in the extracts of yellow snapdragon flowers. Plant Sci. 160 (2001) 229-236. [PMID: 11164594]
4. Ono, E., Fukuchi-Mizutani, M., Nakamura, N., Fukui, Y., Yonekura-Sakakibara, K., Yamaguchi, M., Nakayama, T., Tanaka, T., Kusumi, T. and Tanaka, Y. Yellow flowers generated by expression of the aurone biosynthetic pathway. Proc. Natl. Acad. Sci. USA 103 (2006) 11075-11080. [PMID: 16832053]
Accepted name: tetrahydrocannabinolic acid synthase
Reaction: cannabigerolate + O2 = Δ9-tetrahydrocannabinolate + H2O2
For diagram of reaction click here.
Glossary: Δ9-tetrahydrocannabinolate = Δ9-THCA = (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene-2-carboxylate
cannabigerolate = CBGA = 3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
cannabinerolate = 3-[(2Z)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
Other name(s): THCA synthase; Δ1-tetrahydrocannabinolic acid synthase
Systematic name: cannabigerolate:oxygen oxidoreductase (cyclizing, Δ9-tetrahydrocannabinolate-forming)
Comments: A flavoprotein (FAD). The cofactor is covalently bound. Part of the cannabinoids biosynthetic pathway in the plant Cannabis sativa. The enzyme can also convert cannabinerolate (the (Z)-isomer of cannabigerolate) to Δ9-THCA with lower efficiency. The traditional numbering called Δ9-tetrahydrocannabinolate, Δ1-tetrahydrocannabinolate. Systematic peripheral numbering is now recommended.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Taura, F., Morimoto, S. Shoyama, Y. and Mechoulam, R. First direct evidence for the mechanism of Δ1-tetrahydrocannabinolic acid biosynthesis. J. Am. Chem. Soc. 117 (1995) 9766-9767.
2. Sirikantaramas, S., Morimoto, S., Shoyama, Y., Ishikawa, Y., Wada, Y., Shoyama, Y. and Taura, F. The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of Δ1-tetrahydrocannabinolic acid synthase from Cannabis sativa L. J. Biol. Chem. 279 (2004) 39767-39774. [PMID: 15190053]
3. Shoyama, Y., Takeuchi, A., Taura, F., Tamada, T., Adachi, M., Kuroki, R., Shoyama, Y. and Morimoto, S. Crystallization of Δ1-tetrahydrocannabinolic acid (THCA) synthase from Cannabis sativa. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 799-801. [PMID: 16511162]
4. Shoyama, Y., Tamada, T., Kurihara, K., Takeuchi, A., Taura, F., Arai, S., Blaber, M., Shoyama, Y., Morimoto, S. and Kuroki, R. Structure and function of 1-tetrahydrocannabinolic acid (THCA) synthase, the enzyme controlling the psychoactivity of Cannabis sativa. J. Mol. Biol. (2012) . [PMID: 22766313]
Accepted name: cannabidiolic acid synthase
Reaction: cannabigerolate + O2 = cannabidiolate + H2O2
For diagram of reaction click here.
Glossary: cannabigerolate = CBGA = 3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
cannabidiolate = 2,4-dihydroxy-3-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-6-pentylbenzoate
Other name(s): CBDA synthase
Systematic name: cannabigerolate:oxygen oxidoreductase (cyclizing, cannabidiolate-forming)
Comments: Binds FAD covalently. Part of the cannabinoids biosynthetic pathway of the plant Cannabis sativa. The enzyme can also convert cannabinerolate to cannabidiolate with lower efficiency.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Taura, F., Morimoto, S. and Shoyama, Y. Purification and characterization of cannabidiolic-acid synthase from Cannabis sativa L.. Biochemical analysis of a novel enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid. J. Biol. Chem. 271 (1996) 17411-17416. [PMID: 8663284]
2. Taura, F., Sirikantaramas, S., Shoyama, Y., Yoshikai, K., Shoyama, Y. and Morimoto, S. Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa. FEBS Lett 581 (2007) 2929-2934. [PMID: 17544411]
[EC 1.21.3.9 Transferred entry: dichlorochromopyrrolate synthase, now classified as EC 1.21.98.2, dichlorochromopyrrolate synthase (EC 1.21.3.9 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, deleted 2016)]
Accepted name: hercynylcysteine S-oxide synthase
Reaction: hercynine + L-cysteine + O2 = S-(hercyn-2-yl)-L-cysteine S-oxide + H2O
For diagram of reaction click here
Glossary: hercynine = Nα,Nα,Nα-trimethyl-L-histidine
Other name(s): Egt1; Egt-1
Systematic name: hercynine,L-cysteine:oxygen [S-(hercyn-2-yl)-L-cysteine S-oxide-forming]
Comments: Requires Fe2+ for activity. The enzyme, found in fungal species, is part of a fusion protein that also has the the activity of EC 2.1.1.44, L-histidine Nα-methyltransferase. It is part of the biosynthesis pathway of ergothioneine. The enzyme can also use L-selenocysteine to produce hercynylselenocysteine, which can be converted to selenoneine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Pluskal, T., Ueno, M. and Yanagida, M. Genetic and metabolomic dissection of the ergothioneine and selenoneine biosynthetic pathway in the fission yeast, S. pombe, and construction of an overproduction system. PLoS One 9 (2014) e97774. [PMID: 24828577]
EC 1.21.4.5 tetrachlorohydroquinone reductive dehalogenase
EC 1.21.4.1
Accepted name: D-proline reductase
Reaction: 5-aminopentanoate + a [PrdC protein with a selenide-sulfide bridge] = D-proline + a [PrdC protein with thiol/selenol residues]
For diagram of reaction mechanism click here
Other name(s): prdAB (gene names); D-proline reductase (dithiol)
Systematic name: 5-aminopentanoate:[PrdC protein] oxidoreductase (cyclizing)
Comments: A pyruvoyl- and L-selenocysteine-containing enzyme found in a number of Clostridial species. The pyruvoyl group, located on the PrdA subunit, binds the substrate, while the selenocysteine residue, located on the PrdB subunit, attacks the α-C-atom of D-proline, leading to a reductive cleavage of the C-N-bond of the pyrrolidine ring and formation of a selenoether. The selenoether is cleaved by a cysteine residue of PrdB, resulting in a mixed selenide-sulfide bridge, which is restored to its reduced state by another selenocysteine protein, PrdC. 5-aminopentanoate is released from PrdA by hydrolysis, regenerating the pyruvoyl moiety. The resulting mixed selenide-sulfide bridge in PrdC is reduced by NADH.
Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, CAS registry number: 37255-43-9
References:
1. Stadtman, T.C. and Elliott, P. Studies on the enzymic reduction of amino acids. II. Purification and properties of a D-proline reductase and a proline racemase from Clostridium sticklandii. J. Biol. Chem. 228 (1957) 983-997. [PMID: 13475375]
2. Hodgins, D.S. and Abeles, R.H. Studies of the mechanism of action of D-proline reductase: the presence on covalently bound pyruvate and its role in the catalytic process. Arch. Biochem. Biophys. 130 (1969) 274-285. [PMID: 5778643]
3. Kabisch, U.C., Gräntzdörffer, A., Schierhorn, A., Rücknagel, K.P, Andreesen, J.R. and Pich, A. Identification of D-proline reductase from Clostridium sticklandii as a selenoenzyme and indications for a catalytically active pyruvoyl group derived from a cysteine residue by cleavage of a proprotein. J. Biol. Chem. 274 (1999) 8445-8454. [PMID: 10085076]
4. Bednarski, B., Andreesen, J.R. and Pich, A. In vitro processing of the proproteins GrdE of protein B of glycine reductase and PrdA of D-proline reductase from Clostridium sticklandii: formation of a pyruvoyl group from a cysteine residue. Eur. J. Biochem. 268 (2001) 3538-3544. [PMID: 11422384]
5. Fonknechten, N., Chaussonnerie, S., Tricot, S., Lajus, A., Andreesen, J.R., Perchat, N., Pelletier, E., Gouyvenoux, M., Barbe, V., Salanoubat, M., Le Paslier, D., Weissenbach, J., Cohen, G.N. and Kreimeyer, A. Clostridium sticklandii, a specialist in amino acid degradation: revisiting its metabolism through its genome sequence. BMC Genomics 11 (2010) 555. [PMID: 20937090]
Accepted name: glycine reductase
Reaction: acetyl phosphate + NH3 + thioredoxin disulfide + H2O = glycine + phosphate + thioredoxin
For diagram click here.
Systematic name: acetyl-phosphate ammonia:thioredoxin disulfide oxidoreductase (glycine-forming)
Comments: The reaction is observed only in the direction of glycine reduction. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for glycine binding and ammonia release. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. Only subunit B distinguishes this enzyme from EC 1.21.4.3 (sarcosine reductase) and EC 1.21.4.4 (betaine reductase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 254889-62-8
References:
1. Wagner, M., Sonntag, D., Grimm, R., Pich, A. Eckerskorn, C., Söhling, B. and Andreesen, J.R. Substrate-specific selenoprotein B of glycine reductase from Eubacterium acidaminophilum. Eur. J. Biochem. 260 (1999) 38-49. [PMID: 10091582]
2. Bednarski, B., Andreesen, J.R. and Pich, A. In vitro processing of the proproteins GrdE of protein B of glycine reductase and PrdA of D-proline reductase from Clostridium sticklandii: formation of a pyruvoyl group from a cysteine residue. Eur. J. Biochem. 268 (2001) 3538-3544. [PMID: 11422384]
Accepted name: sarcosine reductase
Reaction: acetyl phosphate + methylamine + thioredoxin disulfide + H2O = N-methylglycine + phosphate + thioredoxin
For diagram click here.
Glossary: sarcosine = N-methylglycine
Systematic name: acetyl-phosphate methylamine:thioredoxin disulfide oxidoreductase (N-methylglycine-forming)
Comments: The reaction is observed only in the direction of sarcosine reduction. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for sarcosine binding and methylamine release. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. Only subunit B distinguishes this enzyme from EC 1.21.4.2 (glycine reductase) and EC 1.21.4.4 (betaine reductase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 125752-88-7
References:
1. Wagner, M., Sonntag, D., Grimm, R., Pich, A. Eckerskorn, C., Söhling, B. and Andreesen, J.R. Substrate-specific selenoprotein B of glycine reductase from Eubacterium acidaminophilum. Eur. J. Biochem. 260 (1999) 38-49. [PMID: 10091582]
2. Hormann, K. and Andreesen, J.R. Reductive cleavage of sarcosine and betaine by Eubacterium acidaminophilum via enzyme systems different from glycine reductase. Arch. Microbiol. 153 (1989) 50-59.
Accepted name: betaine reductase
Reaction: acetyl phosphate + trimethylamine + thioredoxin disulfide + H2O = betaine + phosphate + thioredoxin
For diagram click here.
Glossary: betaine = glycine betaine = N,N,N-trimethylglycine
Other name(s): acetyl-phosphate trimethylamine:thioredoxin disulfide oxidoreductase (N,N,N-trimethylglycine-forming)
Systematic name: acetyl-phosphate trimethylamine:thioredoxin disulfide oxidoreductase (betaine-forming)
Comments: The reaction is observed only in the direction of betaine reduction. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for betaine binding and trimethylamine release. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. Only subunit B distinguishes this enzyme from EC 1.21.4.2 (glycine reductase) and EC 1.21.4.3 (sarcosine reductase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 125752-87-6
References:
1. Wagner, M., Sonntag, D., Grimm, R., Pich, A. Eckerskorn, C., Söhling, B. and Andreesen, J.R. Substrate-specific selenoprotein B of glycine reductase from Eubacterium acidaminophilum. Eur. J. Biochem. 260 (1999) 38-49. [PMID: 10091582]
2. Bednarski, B., Andreesen, J.R. and Pich, A. In vitro processing of the proproteins GrdE of protein B of glycine reductase and PrdA of D-proline reductase from Clostridium sticklandii: formation of a pyruvoyl group from a cysteine residue. Eur. J. Biochem. 268 (2001) 3538-3544. [PMID: 11422384]
Accepted name: tetrachlorohydroquinone reductive dehalogenase
Reaction: (1) 2,6-dichlorohydroquinone + Cl- + glutathione disulfide = 2,3,6-trichlorohydroquinone + 2 glutathione
(2) 2,3,6-trichlorohydroquinone + Cl- + glutathione disulfide = 2,3,5,6-tetrachlorohydroquinone + 2 glutathione
Other name(s): pcpC (gene name)
Systematic name: glutathione disulfide:2,6-dichlorohydroquinone (chlorinating)
Comments: The enzyme, characterized from the bacterium Sphingobium chlorophenolicum, converts tetrachlorohydroquinone to 2,6-dichlorohydroquinone in two steps, via 2,3,6-trichlorohydroquinone, using glutathione as the reducing agent. The enzyme is sensitive to oxidation - when an internal L-cysteine residue is oxidized, the enzyme produces 2,3,5-trichloro-6-(glutathion-S-yl)-hydroquinone and 2,6-dichloro-3-(glutathion-S-yl)-hydroquinone instead of its normal products.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Xun, L., Topp, E. and Orser, C.S. Purification and characterization of a tetrachloro-p-hydroquinone reductive dehalogenase from a Flavobacterium sp. J. Bacteriol. 174 (1992) 8003-8007. [PMID: 1459949]
2. McCarthy, D.L., Navarrete, S., Willett, W.S., Babbitt, P.C. and Copley, S.D. Exploration of the relationship between tetrachlorohydroquinone dehalogenase and the glutathione S-transferase superfamily. Biochemistry 35 (1996) 14634-14642. [PMID: 8931562]
Accepted name: cyclic dehypoxanthinyl futalosine synthase
Reaction: dehypoxanthine futalosine + S-adenosyl-L-methionine = cyclic dehypoxanthinyl futalosine + 5'-deoxyadenosine + L-methionine
For diagram of reaction click here.
Glossary: dehypoxanthine futalosine = 3-{3-[(2R,3S,4R)-3,4,5-trihydroxytetrahydrofuran-2-yl]propanoyl}benzoate
cyclic dehypoxanthinyl futalosine = (2R,3S,4R)-3,4,5-trihydroxy-4'-oxo-3',4,4',5-tetrahydro-2'H,3H-spiro[furan-2,1'-naphthalene]-6'-carboxylate
Other name(s): MqnC; dehypoxanthinyl futalosine cyclase
Systematic name: dehypoxanthine futalosine:S-adenosyl-L-methionine oxidoreductase (cyclizing)
Comments: This enzyme is a member of the ‘AdoMet radical’ (radical SAM) family. The enzyme, found in several bacterial species, is part of the futalosine pathway for menaquinone biosynthesis.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Hiratsuka, T., Furihata, K., Ishikawa, J., Yamashita, H., Itoh, N., Seto, H. and Dairi, T. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321 (2008) 1670-1673. [PMID: 18801996]
2. Cooper, L.E., Fedoseyenko, D., Abdelwahed, S.H., Kim, S.H., Dairi, T. and Begley, T.P. In vitro reconstitution of the radical S-adenosylmethionine enzyme MqnC involved in the biosynthesis of futalosine-derived menaquinone. Biochemistry 52 (2013) 4592-4594. [PMID: 23763543]
Accepted name: dichlorochromopyrrolate synthase
Reaction: 2 3-(7-chloroindol-3-yl)-2-iminopropanoate + H2O2 = dichlorochromopyrrolate + NH3 + 2 H2O
For diagram of reaction click here.
Glossary: dichlorochromopyrrolate = 3,4-bis(7-chloro-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxylate
Other name(s): RebD; chromopyrrolic acid synthase; chromopyrrolate synthase
Systematic name: 3-(7-chloroindol-3-yl)-2-iminopropanoate ammonia-lyase (dichlorochromopyrrolate-forming)
Comments: This enzyme catalyses a step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid produced by the bacterium Lechevalieria aerocolonigenes. The enzyme is a dimeric heme-protein oxidase that catalyses the oxidative dimerization of two L-tryptophan-derived molecules to form dichlorochromopyrrolic acid, the precursor for the fused six-ring indolocarbazole scaffold of rebeccamycin [1]. Contains one molecule of heme b per monomer, as well as non-heme iron that is not part of an iron-sulfur center [2]. In vivo the enzyme uses hydrogen peroxide, formed by the enzyme upstream in the biosynthetic pathway (EC 1.4.3.23, 7-chloro-L-tryptophan oxidase) as the electron acceptor. However, the enzyme is also able to catalyse the reaction using molecular oxygen [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Nishizawa, T., Gruschow, S., Jayamaha, D.H., Nishizawa-Harada, C. and Sherman, D.H. Enzymatic assembly of the bis-indole core of rebeccamycin. J. Am. Chem. Soc. 128 (2006) 724-725. [PMID: 16417354]
2. Howard-Jones, A.R. and Walsh, C.T. Enzymatic generation of the chromopyrrolic acid scaffold of rebeccamycin by the tandem action of RebO and RebD. Biochemistry 44 (2005) 15652-15663. [PMID: 16313168]
3. Spolitak, T. and Ballou, D.P. Evidence for catalytic intermediates involved in generating the chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD. Arch. Biochem. Biophys. 573 (2015) 111-119. [PMID: 25837855]
Accepted name: anaerobic magnesium-protoporphyrin IX monomethyl ester cyclase
Reaction: magnesium-protoporphyrin IX 13-monomethyl ester + 3 S-adenosyl-L-methionine + H2O = 3,8-divinyl protochlorophyllide a + 3 5'-deoxyadenosine + 3 L-methionine (overall reaction)
(1a) magnesium-protoporphyrin IX 13-monomethyl ester + S-adenosyl-L-methionine + H2O = 131-hydroxy-magnesium-protoporphyrin IX 13-monomethyl ester + 5'-deoxyadenosine + L-methionine
(1b) 131-hydroxy-magnesium-protoporphyrin IX 13-monomethyl ester + S-adenosyl-L-methionine = 131-oxo-magnesium-protoporphyrin IX 13-monomethyl ester + 5'-deoxyadenosine + L-methionine
(1c) 131-oxo-magnesium-protoporphyrin IX 13-monomethyl ester + S-adenosyl-L-methionine = 3,8-divinyl protochlorophyllide a + 5'-deoxyadenosine + L-methionine
For diagram of reaction click here.
Other name(s): bchE (gene name); MPE cyclase (ambiguous)
Systematic name: magnesium-protoporphyrin-IX 13-monomethyl ester,S-adenosyl-L-methionine:H2O oxidoreductase (hydroxylating)
Comments: This radical AdoMet enzyme participates in the biosynthesis of chlorophyllide a in anaerobic bacteria, catalysing the formation of an isocyclic ring. Contains a [4Fe-4S] cluster and a cobalamin cofactor. The same transformation is achieved in aerobic organisms by the oxygen-dependent EC 1.14.13.81, magnesium-protoporphyrin IX monomethyl ester (oxidative) cyclase. Some facultative phototrophic bacteria, such as Rubrivivax gelatinosus, possess both enzymes.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Yang, Z.M. and Bauer, C.E. Rhodobacter capsulatus genes involved in early steps of the bacteriochlorophyll biosynthetic pathway. J. Bacteriol. 172 (1990) 5001-5010. [PMID: 2203738]
2. Gough, S.P., Petersen, B.O. and Duus, J.O. Anaerobic chlorophyll isocyclic ring formation in Rhodobacter capsulatus requires a cobalamin cofactor. Proc. Natl. Acad. Sci. USA 97 (2000) 6908-6913. [PMID: 10841582]
3. Ouchane, S., Steunou, A.S., Picaud, M. and Astier, C. Aerobic and anaerobic Mg-protoporphyrin monomethyl ester cyclases in purple bacteria: a strategy adopted to bypass the repressive oxygen control system. J. Biol. Chem. 279 (2004) 6385-6394. [PMID: 14617630]
4. Booker, S.J. Anaerobic functionalization of unactivated C-H bonds. Curr. Opin. Chem. Biol. 13 (2009) 58-73. [PMID: 19297239]
Accepted name: PqqA peptide cyclase
Reaction: a PqqA peptide + S-adenosyl-L-methionine = a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Glossary: PqqA peptide = pyrroloquinoline quinone biosynthesis protein A, a small peptide that provides the precursor for the biosynthesis of the cofactor pyrroloquinoline quinone
Other name(s): pqqE (gene name)
Systematic name: PqqA peptide:S-adenosyl-L-methionine oxidoreductase (cyclizing)
Comments: This bacterial enzyme, which is a member of the radical SAM protein family, catalyses the formation of a C-C bond between C-4 of glutamate and C-3 of tyrosine residues of the PqqA protein (which are separated by three amino acid residues). This is the first enzymic step in the biosynthesis of the bacterial enzyme cofactor pyrroloquinoline quinone (PQQ). The reaction is dependent on the presence of flavodoxin and the accessory protein PqqD.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Wecksler, S.R., Stoll, S., Iavarone, A.T., Imsand, E.M., Tran, H., Britt, R.D. and Klinman, J.P. Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily. Chem. Commun. (Camb.) 46 (2010) 7031-7033. [PMID: 20737074]
2. Latham, J.A., Iavarone, A.T., Barr, I., Juthani, P.V. and Klinman, J.P. PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway. J. Biol. Chem. 290 (2015) 12908-12918. [PMID: 25817994]
3. Barr, I., Latham, J.A., Iavarone, A.T., Chantarojsiri, T., Hwang, J.D. and Klinman, J.P. Demonstration that the radical S-adenosylmethionine (SAM) enzyme PqqE catalyzes de novo carbon-carbon cross-linking within a peptide substrate PqqA in the presence of the peptide chaperone PqqD. J. Biol. Chem. 291 (2016) 8877-8884. [PMID: 26961875]
Accepted name: tetraether lipid synthase
Reaction: (1) 2 a 2,3-bis-O-phytanyl-sn-glycero-phospholipid + 4 S-adenosyl-L-methionine + 2 reduced acceptor = a glycerol dibiphytanyl glycerol tetraether phospholipid + 4 L-methionine + 4 5'-deoxyadenosine + 2 acceptor
(2) a 3-bis-O-phytanyl-sn-glycero-phospholipid + 2 S-adenosyl-L-methionine + reduced acceptor = a macrocyclic archaeol phospholipid + 2 L-methionine + 2 5'-deoxyadenosine + acceptor
Glossary: 2,3-bis-O-phytanyl-sn-glycerol = archaeol
Other name(s): GDGT/MA synthase; GDGT/MAS; tetraether synthase; Tes; Mj0619 (locus name)
Systematic name: a 2,3-bis-O-phytanyl-sn-glycero-phospholipid:S-adenosyl-L-methionine,acceptor oxidoreductase (cyclyzing)
Comments: This archaeal enzyme catalyses a C—C bond formation during the biosynthesis of tetraether lipids. The bond is formed between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). The enzyme does not distinguish whether the two lipids are connected in antiparallel or parallel geometry, resulting in formation of two forms of the product, which are known as caldarchaeol and isocaldarchaeol, respectively. The enzyme can also form macrocyclic archaeol phospholipids by joining the two lipid tails of a single substrate molecule. Even though the reaction shown here describes phospholipid substrates, the enzyme can also act on glycolipids or lipids that contains mixed types of polar head groups. The enzyme is a radical SAM enzyme that contains 3 [4Fe-4S] clusters and one mononuclear rubredoxin-like iron ion, each found in a separate domain. The enzyme uses the 5'-deoxyadenosyl radical to initiate the reaction, which involves the formation of an intermediate bond between the substrate carbon and a sulfur of one of the [4Fe-4S] clusters. Two radicals are needed per C-C bond formed. The source of the required additional electrons is not known.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Zeng, Z., Chen, H., Yang, H., Chen, Y., Yang, W., Feng, X., Pei, H. and Welander, P.V. Identification of a protein responsible for the synthesis of archaeal membrane-spanning GDGT lipids. Nat. Commun. 13 (2022) 1545. [PMID: 35318330]
2. Lloyd, C.T., Iwig, D.F., Wang, B., Cossu, M., Metcalf, W.W., Boal, A.K. and Booker, S.J. Discovery, structure, and mechanism of a tetraether lipid synthase. Nature (2022) . [PMID: 35882349]
Accepted name: β-cyclopiazonate dehydrogenase
Reaction: β-cyclopiazonate + acceptor = α-cyclopiazonate + reduced acceptor
For diagram click here.
Other name(s): β-cyclopiazonate oxidocyclase; β-cyclopiazonic oxidocyclase; β-cyclopiazonate:(acceptor) oxidoreductase (cyclizing)
Systematic name: β-cyclopiazonate:acceptor oxidoreductase (cyclizing)
Comments: A flavoprotein (FAD). Cytochrome c and various dyes can act as acceptor. Cyclopiazonate is a microbial toxin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9059-00-1
References:
1. Edmondson, D.E., Kenney, W.C. and Singer, T.P. Structural elucidation and properties of 8α-(N1-histidyl)riboflavin: the flavin component of thiamine dehydrogenase and β-cyclopiazonate oxidocyclase. Biochemistry 15 (1976) 2937-2945. [PMID: 8076]
2. Schabort, J.C. and Potgieter, D.J.J. β-Cyclopiazonate oxidocyclase from Penicillium cyclopium. II. Studies on electron acceptors, inhibitors, enzyme kinetics, amino acid composition, flavin prosthetic group and other properties. Biochim. Biophys. Acta 250 (1971) 329-345. [PMID: 5143340]
[EC 1.21.99.2 Transferred entry: EC 1.21.99.2, cyclic dehypoxanthinyl futalosine synthase. Now classified as EC 1.21.98.1, cyclic dehypoxanthinyl futalosine synthase. (EC 1.21.99.2 created 2014, deleted 2014)]
Accepted name: thyroxine 5-deiodinase
Reaction: 3,3',5'-triiodo-L-thyronine + iodide + acceptor + H+ = L-thyroxine + reduced acceptor
Other name(s): diiodothyronine 5'-deiodinase (ambiguous); iodothyronine 5-deiodinase; iodothyronine inner ring monodeiodinase; type III iodothyronine deiodinase
Systematic name: 3,3',5'-triiodo-L-thyronine,iodide:acceptor oxidoreductase (iodinating)
Comments: The enzyme activity has only been demonstrated in the direction of 5-deiodination. This removal of the 5-iodine, i.e. from the inner ring, largely inactivates the hormone thyroxine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Chopra, I.J. and Teco, G.N.C. Characteristics of inner ring (3 or 5) monodeiodination of 3,5-diiodothyronine in rat liver: evidence suggesting marked similarities of inner and outer ring deiodinases for iodothyronines. Endocrinology 110 (1982) 89-97. [PMID: 7053997]
2. Körhle, J. Iodothyronine deiodinases. Methods Enzymol. 347 (2002) 125-167. [PMID: 11898402]
Accepted name: thyroxine 5'-deiodinase
Reaction: 3,3',5-triiodo-L-thyronine + iodide + acceptor + H+ = L-thyroxine + reduced acceptor
Glossary: 3,3',5-triiodo-L-thyronine = O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-L-tyrosine
L-thyroxine = O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine
Other name(s): diiodothyronine 5'-deiodinase [ambiguous]; iodothyronine 5'-deiodinase; iodothyronine outer ring monodeiodinase; type I iodothyronine deiodinase; type II iodothyronine deiodinase; thyroxine 5-deiodinase [misleading]; L-thyroxine iodohydrolase (reducing)
Systematic name: 3,3',5-triiodo-L-thyronine,iodide:acceptor oxidoreductase (iodinating)
Comments: The enzyme activity has only been demonstrated in the direction of 5'-deiodination, which renders the thyroid hormone more active. The enzyme consists of type I and type II enzymes, both containing selenocysteine, but with different kinetics. For the type I enzyme the first reaction is a reductive deiodination converting the -Se-H group of the enzyme into an -Se-I group; the reductant then reconverts this into -Se-H, releasing iodide.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Chopra, I.J. and Teco, G.N.C. Characteristics of inner ring (3 or 5) monodeiodination of 3,5-diiodothyronine in rat liver: evidence suggesting marked similarities of inner and outer ring deiodinases for iodothyronines. Endocrinology 110 (1982) 89-97. [PMID: 7053997]
2. Goswani, A., Leonard, J.L. and Rosenberg, I.N. Inhibition by coumadin anticoagulants of enzymatic outer ring monodeiodination of iodothyronines. Biochem. Biophys. Res. Commun. 104 (1982) 1231-1238. [PMID: 6176242]
3. Smallridge, R.C., Burman, K.D., Ward, K.E., Wartofsky, L., Dimond, R.C., Wright, F.D. and Lathan, K.R. 3',5'-Diiodothyronine to 3'-monoiodothyronine conversion in the fed and fasted rat: enzyme characteristics and evidence for two distinct 5'-deiodinases. Endocrinology 108 (1981) 2336-2345. [PMID: 7227308]
4. Körhle, J. Iodothyronine deiodinases. Methods Enzymol. 347 (2002) 125-167. [PMID: 11898402]
Accepted name: tetrachloroethene reductive dehalogenase
Reaction: trichloroethene + chloride + acceptor = tetrachloroethene + reduced acceptor
Glossary: methyl viologen = 1,1'-dimethyl-4,4'-bipyridin-1,1'-diium
Other name(s): tetrachloroethene reductase
Systematic name: acceptor:trichloroethene oxidoreductase (chlorinating)
Comments: This enzyme allows the common pollutant tetrachloroethene to support bacterial growth and is responsible for disposal of a number of chlorinated hydrocarbons. The reaction occurs in the reverse direction. The enzyme also reduces trichloroethene to dichloroethene. Although the physiological reductant is unknown, the supply of reductant in some organisms involves menaquinol, which is reduced by molecular hydrogen via the action of EC 1.12.5.1, hydrogen:quinone oxidoreductase. The enzyme contains a corrinoid and two iron-sulfur clusters. Methyl viologen can act as electron donor in vitro.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Holliger, C, Wohlfarth, G. and Diekert, G. Reductive dechlorination in the energy metabolism of anaerobic bacteria. FEMS Microbiol. Rev. 22 (1998) 383-398.
2. Glod, G., Angst, W., Holliger, C. and Schwarzenbach, R.P. Corrinoid-mediated reduction of tetrachloroethene, trichloroethene, and trichlorofluoroethene in homogeneous aqueous solution: Reaction kinetics and reaction mechanisms. Environ. Sci. Technol. 31 (1997) 253-260.
3. Neumann, A., Wohlfarth, G. and Diekert, G. Purification and characterization of tetrachloroethene reductive dehalogenase from Dehalospirillum multivorans.J. Biol. Chem. 271 (1996) 16515-16519. [PMID: 8663199]
4. Schumacher, W., Holliger, C., Zehnder, A.J.B. and Hagen, W.R. Redox chemistry of cobalamin and iron-sulfur cofactors in the tetrachloroethene reductase of Dehalobacter restrictus. FEBS Lett. 409 (1997) 421-425. [PMID: 9224702]
5. Schumacher, W. and Holliger, C. The proton/electron ratio of the menaquinone-dependent electron transport from dihydrogen to tetrachloroethene in "Dehalobacter restrictus". J. Bacteriol. 178 (1996) 2328-2333. [PMID: 8636034]
EC 1.22.1 With NAD+ or NADP+ as acceptor
[EC 1.22.1.1 Transferred entry: iodotyrosine deiodinase. Now EC 1.21.1.1, iodotyrosine deiodinase (EC 1.22.1.1 created 2010, deleted 2015)]
Sections
EC 1.23.1 With NADH or NADPH as donor
EC 1.23.5 With a quinone or related compound as acceptor
Accepted name: (+)-pinoresinol reductase
Reaction: (+)-lariciresinol + NADP+ = (+)-pinoresinol + NADPH + H+
For diagram of reaction click here.
Glossary: (+)-lariciresinol = 4-[(2S,3R,4R)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)oxolan-2-yl]-2-methoxyphenol
(+)-pinoresinol = (1S,3aR,4S,6aR)-4,4-(tetrahydro-1H,3H-furo[3,4-c]furan-1,4-diyl)bis(2-methoxyphenol)
Other name(s): pinoresinol/lariciresinol reductase; pinoresinol-lariciresinol reductases; (+)-pinoresinol/(+)-lariciresinol; (+)-pinoresinol-(+)-lariciresinol reductase; PLR
Systematic name: (+)-lariciresinol:NADP+ oxidoreductase
Comments: The reaction is catalysed in vivo in the opposite direction to that shown. A multifunctional enzyme that further reduces the product to the lignan (–)-secoisolariciresinol [EC 1.23.1.2, (+)-lariciresinol reductase]. Isolated from the plants Forsythia intermedia [1,2], Thuja plicata (western red cedar) [3], Linum perenne (perennial flax) [5] and Linum corymbulosum [6]. The 4-pro-R hydrogen of NADH is transferred to the 7-pro-R position of lariciresinol [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Chu, A., Dinkova, A., Davin, L.B., Bedgar, D.L. and Lewis, N.G. Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia. J. Biol. Chem. 268 (1993) 27026-27033. [PMID: 8262939]
2. Dinkova-Kostova, A.T., Gang, D.R., Davin, L.B., Bedgar, D.L., Chu, A. and Lewis, N.G. (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia. Protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase. J. Biol. Chem. 271 (1996) 29473-29482. [PMID: 8910615]
3. Fujita, M., Gang, D.R., Davin, L.B. and Lewis, N.G. Recombinant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274 (1999) 618-627. [PMID: 9872995]
4. Min, T., Kasahara, H., Bedgar, D.L., Youn, B., Lawrence, P.K., Gang, D.R., Halls, S.C., Park, H., Hilsenbeck, J.L., Davin, L.B., Lewis, N.G. and Kang, C. Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases. J. Biol. Chem. 278 (2003) 50714-50723. [PMID: 13129921]
5. Hemmati, S., Schmidt, T.J. and Fuss, E. (+)-Pinoresinol/(–)-lariciresinol reductase from Linum perenne Himmelszelt involved in the biosynthesis of justicidin B. FEBS Lett. 581 (2007) 603-610. [PMID: 17257599]
6. Bayindir, Ü., Alfermann, A.W. and Fuss, E. Hinokinin biosynthesis in Linum corymbulosum Reichenb. Plant J. 55 (2008) 810-820. [PMID: 18489708]
Accepted name: (+)-lariciresinol reductase
Reaction: (–)-secoisolariciresinol + NADP+ = (+)-lariciresinol + NADPH + H+
For diagram of reaction click here.
Glossary: (+)-lariciresinol = 4-[(2S,3R,4R)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)oxolan-2-yl]-2-methoxyphenol
(–)-secoisolariciresinol = (2R,3R)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]butane-1,4-diol
Other name(s): pinoresinol/lariciresinol reductase; pinoresinol-lariciresinol reductases; (+)-pinoresinol/(+)-lariciresinol; (+)-pinoresinol-(+)-lariciresinol reductase; PLR
Systematic name: (–)-secoisolariciresinol:NADP+ oxidoreductase
Comments: The reaction is catalysed in vivo in the opposite direction to that shown. A multifunctional enzyme that also reduces (+)-pinoresinol [EC 1.23.1.1, (+)-pinoresinol reductase]. Isolated from the plants Forsythia intermedia [1,2], Thuja plicata (western red cedar) [3], Linum perenne (perennial flax) [5] and Linum corymbulosum [6].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Chu, A., Dinkova, A., Davin, L.B., Bedgar, D.L. and Lewis, N.G. Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia. J. Biol. Chem. 268 (1993) 27026-27033. [PMID: 8262939]
2. Dinkova-Kostova, A.T., Gang, D.R., Davin, L.B., Bedgar, D.L., Chu, A. and Lewis, N.G. (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia. Protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase. J. Biol. Chem. 271 (1996) 29473-29482. [PMID: 8910615]
3. Fujita, M., Gang, D.R., Davin, L.B. and Lewis, N.G. Recombinant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274 (1999) 618-627. [PMID: 9872995]
4. Min, T., Kasahara, H., Bedgar, D.L., Youn, B., Lawrence, P.K., Gang, D.R., Halls, S.C., Park, H., Hilsenbeck, J.L., Davin, L.B., Lewis, N.G. and Kang, C. Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases. J. Biol. Chem. 278 (2003) 50714-50723. [PMID: 13129921]
5. Hemmati, S., Schmidt, T.J. and Fuss, E. (+)-Pinoresinol/(–)-lariciresinol reductase from Linum perenne Himmelszelt involved in the biosynthesis of justicidin B. FEBS Lett. 581 (2007) 603-610. [PMID: 17257599]
6. Bayindir, Ü., Alfermann, A.W. and Fuss, E. Hinokinin biosynthesis in Linum corymbulosum Reichenb. Plant J. 55 (2008) 810-820. [PMID: 18489708]
Accepted name: (–)-pinoresinol reductase
Reaction: (–)-lariciresinol + NADP+ = (–)-pinoresinol + NADPH + H+
For diagram of reaction click here.
Glossary: (–)-lariciresinol = 4-[(2R,3S,4S)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)oxolan-2-yl]-2-methoxyphenol
(–)-pinoresinol = (1R,3aS,4R,6aS)-4,4'-(tetrahydro-1H,3H-furo[3,4-c]furan-1,4-diyl)bis(2-methoxyphenol)
Other name(s): pinoresinol/lariciresinol reductase; pinoresinol-lariciresinol reductases; (–)-pinoresinol-(–)-lariciresinol reductase; PLR
Systematic name: (–)-lariciresinol:NADP+ oxidoreductase
Comments: The reaction is catalysed in vivo in the opposite direction to that shown. A multifunctional enzyme that usually further reduces the product to (+)-secoisolariciresinol [EC 1.23.1.4, (–)-lariciresinol reductase]. Isolated from the plants Thuja plicata (western red cedar) [1], Linum perenne (perennial flax) [2] and Arabidopsis thaliana (thale cress) [3].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Fujita, M., Gang, D.R., Davin, L.B. and Lewis, N.G. Recombinant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274 (1999) 618-627. [PMID: 9872995]
2. Hemmati, S., Schmidt, T.J. and Fuss, E. (+)-Pinoresinol/(–)-lariciresinol reductase from Linum perenne Himmelszelt involved in the biosynthesis of justicidin B. FEBS Lett. 581 (2007) 603-610. [PMID: 17257599]
3. Nakatsubo, T., Mizutani, M., Suzuki, S., Hattori, T. and Umezawa, T. Characterization of Arabidopsis thaliana pinoresinol reductase, a new type of enzyme involved in lignan biosynthesis. J. Biol. Chem. 283 (2008) 15550-15557. [PMID: 18347017]
Accepted name: (–)-lariciresinol reductase
Reaction: (+)-secoisolariciresinol + NADP+ = (–)-lariciresinol + NADPH + H+
For diagram of reaction click here.
Glossary: (–)-lariciresinol = 4-[(2R,3S,4S)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)oxolan-2-yl]-2-methoxyphenol
(+)-secoisolariciresinol = (2S,3S)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]butane-1,4-diol
Other name(s): pinoresinol/lariciresinol reductase; pinoresinol-lariciresinol reductases; (–)-pinoresinol-(–)-lariciresinol reductase; PLR
Systematic name: (+)-secoisolariciresinol:NADP+ oxidoreductase
Comments: The reaction is catalysed in vivo in the opposite direction to that shown. A multifunctional enzyme that also reduces (–)-pinoresinol [EC 1.23.1.3, (–)-pinoresinol reductase]. Isolated from the plants Thuja plicata (western red cedar) [1] and Linum corymbulosum [2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Fujita, M., Gang, D.R., Davin, L.B. and Lewis, N.G. Recombinant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274 (1999) 618-627. [PMID: 9872995]
2. Hemmati, S., Schmidt, T.J. and Fuss, E. (+)-Pinoresinol/(–)-lariciresinol reductase from Linum perenne Himmelszelt involved in the biosynthesis of justicidin B. FEBS Lett. 581 (2007) 603-610. [PMID: 17257599]
Accepted name: violaxanthin de-epoxidase
Reaction: violaxanthin + 2 L-ascorbate = zeaxanthin + 2 L-dehydroascorbate + 2 H2O (overall reaction)
(1a) violaxanthin + L-ascorbate = antheraxanthin + L-dehydroascorbate + H2O
(1b) antheraxanthin + L-ascorbate = zeaxanthin + L-dehydroascorbate + H2O
For diagram of reaction click here.
Glossary: violaxanthin = (3S,3'S,5R,5'R,6S,6'S)-5,6:5',6'-diepoxy-5,5',6,6'-tetrahydro-β,β-carotene-3,3'-diol
antheraxanthin = (3R,3'S,5'R,6'S)-5',6'-epoxy-5',6'-dihydro-β,β-carotene-3,3'-diol
zeaxanthin = (3R,3'R)-β,β-carotene-3,3'-diol
Other name(s): VDE
Systematic name: violaxanthin:ascorbate oxidoreductase
Comments: Along with EC 1.14.15.21, zeaxanthin epoxidase, this enzyme forms part of the xanthophyll (or violaxanthin) cycle for controlling the concentration of zeaxanthin in chloroplasts. It is activated by a low pH of the thylakoid lumen (produced by high light intensity). Zeaxanthin induces the dissipation of excitation energy in the chlorophyll of the light-harvesting protein complex of photosystem II. In higher plants the enzyme reacts with all-trans-diepoxides, such as violaxanthin, and all-trans-monoepoxides, but in the alga Mantoniella squamata, only the diepoxides are good substrates.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Yamamoto, H.Y. and Higashi, R.M. Violaxanthin de-epoxidase. Lipid composition and substrate specificity. Arch. Biochem. Biophys. 190 (1978) 514-522. [PMID: 102251]
2. Rockholm, D.C. and Yamamoto, H.Y. Violaxanthin de-epoxidase. Plant Physiol. 110 (1996) 697-703. [PMID: 8742341]
3. Bugos, R.C., Hieber, A.D. and Yamamoto, H.Y. Xanthophyll cycle enzymes are members of the lipocalin family, the first identified from plants. J. Biol. Chem. 273 (1998) 15321-15324. [PMID: 9624110]
4. Kuwabara, T., Hasegawa, M., Kawano, M. and Takaichi, S. Characterization of violaxanthin de-epoxidase purified in the presence of Tween 20: effects of dithiothreitol and pepstatin A. Plant Cell Physiol. 40 (1999) 1119-1126. [PMID: 10635115]
5. Latowski, D., Kruk, J., Burda, K., Skrzynecka-Jaskierm, M., Kostecka-Gugala, A. and Strzalka, K. Kinetics of violaxanthin de-epoxidation by violaxanthin de-epoxidase, a xanthophyll cycle enzyme, is regulated by membrane fluidity in model lipid bilayers. Eur. J. Biochem. 269 (2002) 4656-4665. [PMID: 12230579]
6. Goss, R. Substrate specificity of the violaxanthin de-epoxidase of the primitive green alga Mantoniella squamata (Prasinophyceae). Planta 217 (2003) 801-812. [PMID: 12748855]
7. Latowski, D., Akerlund, H.E. and Strzalka, K. Violaxanthin de-epoxidase, the xanthophyll cycle enzyme, requires lipid inverted hexagonal structures for its activity. Biochemistry 43 (2004) 4417-4420. [PMID: 15078086]
Accepted name: chlorate reductase
Reaction: reduced acceptor + chlorate = acceptor + H2O + chlorite
Other name(s): chlorate reductase C
Systematic name: chlorite:acceptor oxidoreductase
Comments: Flavins or benzyl viologen can act as acceptor.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 60382-73-2
References:
1. Azoulay, E., Mutaftshiev, S. and de Sousa, M.L. Étude des mutants chlorate-résistants chez Escherichia coli K12. III. Mise en évidence et étude de l'activité chlorate-réductase c des mutants chlC-. Biochim. Biophys. Acta 237 (1971) 579-590. [PMID: 4940765]
Accepted name: pyrogallol hydroxytransferase
Reaction: 1,2,3,5-tetrahydroxybenzene + 1,2,3-trihydroxybenzene = 1,3,5-trihydroxybenzene + 1,2,3,5-tetrahydroxybenzene
Other name(s): 1,2,3,5-tetrahydroxybenzene hydroxyltransferase; 1,2,3,5-tetrahydroxybenzene:pyrogallol transhydroxylase; 1,2,3,5-tetrahydroxybenzene-pyrogallol hydroxyltransferase (transhydroxylase); pyrogallol hydroxyltransferase; 1,2,3,5-tetrahydroxybenzene:1,2,3-trihydroxybenzene hydroxyltransferase
Systematic name: 1,2,3,5-tetrahydroxybenzene:1,2,3-trihydroxybenzene hydroxytransferase
Comments: 1,2,3,5-Tetrahydroxybenzene acts as a co-substrate for the conversion of pyrogallol into phloroglucinol, and for a number of similar isomerizations. The enzyme is provisionally listed here, but might be considered as the basis for a new class in the transferases, analogous to the aminotransferases.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 176591-26-7
References:
1. Brune, A. and Schink, B. Pyrogallol-to-phloroglucinol conversion and other hydroxyl-transfer reactions catalyzed by cell extracts of Pelobacter acidigallici. J. Bacteriol. 172 (1990) 1070-1076. [PMID: 2298693]
[EC 1.97.1.3 Transferred entry: sulfur reductase. Now EC 1.12.98.4, sulfhydrogenase, since hydrogen is known to be the electron donor. (EC 1.97.1.3 created 1992, deleted 2013)]
Accepted name: [formate-C-acetyltransferase]-activating enzyme
Reaction: S-adenosyl-L-methionine + dihydroflavodoxin + [formate C-acetyltransferase]-glycine = 5'-deoxyadenosine + L-methionine + flavodoxin semiquinone + [formate C-acetyltransferase]-glycin-2-yl radical
Other name(s): PFL activase; PFL-glycine:S-adenosyl-L-methionine H transferase (flavodoxin-oxidizing, S-adenosyl-L-methionine-cleaving); formate acetyltransferase activating enzyme; formate acetyltransferase-glycine dihydroflavodoxin:S-adenosyl-L-methionine oxidoreductase (S-adenosyl-L-methionine cleaving); pyruvate formate-lyase activating enzyme; pyruvate formate-lyase 1 activating enzyme
Systematic name: [formate C-acetyltransferase]-glycine dihydroflavodoxin:S-adenosyl-L-methionine oxidoreductase (S-adenosyl-L-methionine cleaving)
Comments: An iron-sulfur protein. A single glycine residue in EC 2.3.1.54, formate C-acetyltransferase, is oxidized to the corresponding radical by transfer of H from its CH2 to AdoMet with concomitant cleavage of the latter. The reaction requires Fe2+. The first stage is reduction of the AdoMet to give methionine and the 5'-deoxyadenosin-5'-yl radical, which then abstracts a hydrogen radical from the glycine residue.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 206367-15-9
References:
1. Frey, M., Rothe, M., Wagner, A.F.V. and Knappe, J. Adenosylmethionine-dependent synthesis of the glycyl radical in pyruvate formate-lyase by abstraction of the glycine C-2 pro-S hydrogen atom. J. Biol. Chem. 269 (1994) 12432-12437. [PMID: 8175649]
2. Wagner, A.F.V., Frey, M., Neugebauer, F.A., Schäfer, W. and Knappe, J. The free radical in pyruvate formate-lyase is located on glycine-734. Proc. Natl. Acad. Sci. USA 89 (1992) 996-1000. [PMID: 1310545]
3. Frey, P.A. Radical mechanisms in enzymatic catalysis. Annu. Rev. Biochem. 70 (2001) 121-148. [PMID: 11395404]
[EC 1.97.1.5 Transferred entry: now EC 1.20.4.1, arsenate reductase (glutaredoxin) (EC 1.97.1.5 created 2000 deleted 2001)]
[EC 1.97.1.6 Transferred entry: now EC 1.20.99.1, arsenate reductase (donor) (EC 1.97.1.6 created 2000 deleted 2001)]
[EC 1.97.1.7 Transferred entry: now EC 1.20.4.2, methylarsonate reductase (EC 1.97.1.7 created 2000, deleted 2001)]
[EC 1.97.1.8 Transferred entry: tetrachloroethene reductive dehalogenase. Now EC 1.21.99.5, tetrachloroethene reductive dehalogenase (EC 1.97.1.8 created 2001, deleted 2017)]
Accepted name: selenate reductase
Reaction: selenite + H2O + acceptor = selenate + reduced acceptor
Systematic name: selenite:reduced acceptor oxidoreductase
Comments: The periplasmic enzyme from Thauera selenatis is a complex comprising three heterologous subunits (α, β and γ) that contains molybdenum, iron, acid-labile sulfide and heme b as cofactor constituents. Nitrate, nitrite, chlorate and sulfate are not substrates. A number of compounds, including acetate, lactate, pyruvate, and certain sugars, amino acids, fatty acids, di- and tricarboxylic acids, and benzoate can serve as electron donors.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 146359-71-9
References:
1. Schröder, I., Rech, S., Krafft, T. and Macy, J.M. Purification and characterization of the selenate reductase from Thauera selenatis. J. Biol. Chem. 272 (1997) 23765-23768. [PMID: 9295321]
2. Macy, J.M., Rech, S., Auling, G., Dorsch, M., Stackebrandt, E. and Sly, L.I. Thauera selenatis gen. nov., sp. nov., a member of the beta subclass of Proteobacteria with a novel type of anaerobic respiration. Int. J. Syst. Bacteriol. 43 (1993) 135-142. [PMID: 8427805]
3. Krafft, T., Bowen, A., Theis, F. and Macy, J.M. Cloning and sequencing of the genes encoding the periplasmic-cytochrome B-containing selenate reductase of Thauera selenatis. DNA Seq. 10 (2000) 365-377. [PMID: 10826693]
4. Stolz, J.F. and Oremland, R.S. Bacterial respiration of arsenic and selenium. FEMS Microbiol. Rev. 23 (1999) 615-627. [PMID: 10525169]
[EC 1.97.1.10 Transferred entry: thyroxine 5-deiodinase. Now EC 1.21.99.4, thyroxine 5-deiodinase (EC 1.97.1.10 created 1984 as EC 3.8.1.4, transferred 2003 to EC 1.97.1.10, deleted 2015)]
[EC 1.97.1.11 Transferred entry: thyroxine 5-deiodinase. Now EC 1.21.99.3 thyroxine 5-deiodinase. (EC 1.97.1.11 created 2003, deleted 2015)]
Accepted name: photosystem I
Reaction: reduced plastocyanin + oxidized ferredoxin + hν = oxidized plastocyanin + reduced ferredoxin
Systematic name: plastocyanin:ferredoxin oxidoreductase (light-dependent)
Comments: Contains chlorophyll, phylloquinones, carotenoids and [4Fe-4S] clusters. Cytochrome c6 can act as an alternative electron donor, and flavodoxin as an alternative acceptor in some species.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Takabe, T., Iwasaki, Y., Hibino, T. and Ando, T. Subunit composition of photosystem I complex that catalyzes light-dependent transfer of electrons from plastocyanin to ferredoxin. J. Biochem. 110 (1991) 622-627. [PMID: 1778985]
2. van Thor, J.J., Geerlings, T.H., Matthijs, H.C. and Hellingwerf, K.J. Kinetic evidence for the PsaE-dependent transient ternary complex photosystem I/Ferredoxin/Ferredoxin:NADP+ reductase in a cyanobacterium. Biochemistry 38 (1999) 12735-12746. [PMID: 10504244]
3. Chitnis, P.R. Photosystem I: function and physiology. Annu. Rev. Plant Physiol. Plant Mol. Biol. 52 (2001) 593-626. [PMID: 11337410]
4. Amunts, A., Toporik, H., Borovikova, A. and Nelson, N. Structure determination and improved model of plant photosystem I. J. Biol. Chem. 285 (2010) 3478-3486. [PMID: 19923216]