An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: L-galactonate 5-dehydrogenase
Reaction: L-galactonate + NAD+ = D-tagaturonate + NADH + H+
Other name(s): lgoD (gene name); lgaC (gene name)
Systematic name: L-galactonate:NAD+ 5-oxidoreductase
Comments: The enzyme, reported from the human gut bacteria Escherichia coli and Bacteroides vulgatus, participates in an L-galactonate degradation pathway.
References:
1. Cooper, R.A. The pathway for L-galactonate catabolism in Escherichia coli K-12. FEBS Lett. 103 (1979) 216-220. [PMID: 381020]
2. Kuivanen, J. and Richard, P. The yjjN of E. coli codes for an L-galactonate dehydrogenase and can be used for quantification of L-galactonate and L-gulonate. Appl. Biochem. Biotechnol. 173 (2014) 1829-1835. [PMID: 24861318]
3. Hobbs, M.E., Williams, H.J., Hillerich, B., Almo, S.C. and Raushel, F.M. L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53 (2014) 4661-4670. [PMID: 24963813]
[EC 1.6.1.5 Transferred entry: proton-translocating NAD(P)+ transhydrogenase. Now EC 7.1.1.1, proton-translocating NAD(P)+ transhydrogenase (EC 1.6.1.5 created 2015, deleted 2018)]
[EC 1.6.5.3 Transferred entry: NADH:ubiquinone reductase (H+-translocating). Now EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating) (EC 1.6.5.3 created 1961, deleted 1965, reinstated 1983, modified 2011, modified 2013, deleted 2018)]
[EC 1.6.5.8 Transferred entry: NADH:ubiquinone reductase (Na+-transporting). Now EC 7.2.1.1, NADH:ubiquinone reductase (Na+-transporting) (EC 1.6.5.8 created 2011, deleted 2018)]
Accepted name: 5-aminosalicylate 1,2-dioxygenase
Reaction: 5-aminosalicylate + O2 = (2Z,4E)-4-amino-6-oxohepta-2,4-dienedioate
Glossary: 5-aminosalicylate = 5-amino-2-hydroxybenzoate
Other name(s): mabB (gene name)
Systematic name: 5-aminosalicylate:oxygen 1,2-oxidoreductase (ring-opening)
Comments: Requires Fe(II). The enzyme, characterized from different bacteria, is a nonheme iron dioxygenase in the bicupin family.
References:
1. Stolz, A., Nortemann, B. and Knackmuss, H.J. Bacterial metabolism of 5-aminosalicylic acid. Initial ring cleavage. Biochem. J. 282 (1992) 675-680. [PMID: 1554350]
2. Yu, H., Zhao, S. and Guo, L. Novel gene encoding 5-aminosalicylate 1,2-dioxygenase from Comamonas sp. strain QT12 and catalytic properties of the purified enzyme. J. Bacteriol. 200 (2018) . [PMID: 29038259]
[EC 1.14.13.125 Transferred entry: tryptophan N-monooxygenase. Now EC 1.14.14.156, tryptophan N-monooxygenase (EC 1.14.13.125 created 2011, deleted 2018)]
[EC 1.14.13.138 Transferred entry: indolin-2-one monooxygenase. Now EC 1.14.14.157, indolin-2-one monooxygenase (EC 1.14.13.138 created 2012, deleted 2018)]
Accepted name: 3,6-diketocamphane 1,2-monooxygenase
Reaction: (–)-bornane-2,5-dione + O2 + FMNH2 = (–)-5-oxo-1,2-campholide + FMN + H2O
Glossary: (–)-bornane-2,5-dione = 3,6-diketocamphane
Other name(s): 3,6-diketocamphane lactonizing enzyme; 3,6-DKCMO
Systematic name: (–)-bornane-2,5-dione,FMNH2:oxygen oxidoreductase (1,2-lactonizing)
Comments: A Baeyer-Villiger monooxygenase isolated from camphor-grown strains of Pseudomonas putida and encoded on the cam plasmid. Involved in the degradation of (–)-camphor. Requires a dedicated NADH-FMN reductase [cf. EC 1.5.1.42, FMN reductase (NADH)] [1-2]. The product spontaneously converts to [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate.
References:
1. Iwaki, H., Grosse, S., Bergeron, H., Leisch, H., Morley, K., Hasegawa, Y. and Lau, P.C. Camphor pathway redux: functional recombinant expression of 2,5- and 3,6-diketocamphane monooxygenases of Pseudomonas putida ATCC 17453 with their cognate flavin reductase catalyzing Baeyer-Villiger reactions. Appl. Environ. Microbiol. 79 (2013) 3282-3293. [PMID: 23524667]
2. Isupov, M.N., Schroder, E., Gibson, R.P., Beecher, J., Donadio, G., Saneei, V., Dcunha, S.A., McGhie, E.J., Sayer, C., Davenport, C.F., Lau, P.C., Hasegawa, Y., Iwaki, H., Kadow, M., Balke, K., Bornscheuer, U.T., Bourenkov, G. and Littlechild, J.A. The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Acta Crystallogr. D Biol. Crystallogr. 71 (2015) 2344-2353. [PMID: 26527149]
Accepted name: tryptophan N-monooxygenase
Reaction: L-tryptophan + 2 [reduced NADPH—hemoprotein reductase] + 2 O2 = (E)-indol-3-ylacetaldoxime + 2 [oxidized NADPH—hemoprotein reductase] + CO2 + 3 H2O (overall reaction)
(1a) L-tryptophan + [reduced NADPH—hemoprotein reductase] + O2 = N-hydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) N-hydroxy-L-tryptophan + [reduced NADPH—hemoprotein reductase] + O2 = N,N-dihydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H2O
(1c) N,N-dihydroxy-L-tryptophan = (E)-indol-3-ylacetaldoxime + CO2 + H2O
Other name(s): tryptophan N-hydroxylase; CYP79B1; CYP79B2; CYP79B3
Systematic name: L-tryptophan,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein from the plant Arabidopsis thaliana. This enzyme catalyses two successive N-hydroxylations of L-tryptophan, the first steps in the biosynthesis of both auxin and the indole alkaloid phytoalexin camalexin. The product of the two hydroxylations, N,N-dihydroxy-L-tryptophan, is extremely labile and dehydrates spontaneously. The dehydrated product is then subject to a decarboxylation that produces an oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme.
References:
1. Mikkelsen, M.D., Hansen, C.H., Wittstock, U. and Halkier, B.A. Cytochrome P450 CYP79B2 from Arabidopsis catalyzes the conversion of tryptophan to indole-3-acetaldoxime, a precursor of indole glucosinolates and indole-3-acetic acid. J. Biol. Chem. 275 (2000) 33712-33717. [PMID: 10922360]
2. Hull, A.K., Vij, R. and Celenza, J.L. Arabidopsis cytochrome P450s that catalyze the first step of tryptophan-dependent indole-3-acetic acid biosynthesis. Proc. Natl. Acad. Sci. USA 97 (2000) 2379-2384. [PMID: 10681464]
3. Zhao, Y., Hull, A.K., Gupta, N.R., Goss, K.A., Alonso, J., Ecker, J.R., Normanly, J., Chory, J. and Celenza, J.L. Trp-dependent auxin biosynthesis in Arabidopsis: involvement of cytochrome P450s CYP79B2 and CYP79B3. Genes Dev. 16 (2002) 3100-3112. [PMID: 12464638]
4. Naur, P., Hansen, C.H., Bak, S., Hansen, B.G., Jensen, N.B., Nielsen, H.L. and Halkier, B.A. CYP79B1 from Sinapis alba converts tryptophan to indole-3-acetaldoxime. Arch. Biochem. Biophys. 409 (2003) 235-241. [PMID: 12464264]
Accepted name: indolin-2-one monooxygenase
Reaction: indolin-2-one + [reduced NADPH—hemoprotein reductase] + O2 = 3-hydroxyindolin-2-one + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Other name(s): BX3 (gene name); CYP71C2 (gene name)
Systematic name: indolin-2-one,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme is involved in the biosynthesis of protective and allelophatic benzoxazinoids in some plants, most commonly from the family of Poaceae (grasses).
References:
1. Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696-699. [PMID: 9235894]
2. Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925-930. [PMID: 10385992]
Accepted name: carotenoid ε hydroxylase
Reaction: (1) α-carotene + [reduced NADPH-hemoprotein reductase] + O2 = α-cryptoxanthin + [oxidized NADPH-hemoprotein reductase] + H2O
(2) zeinoxanthin + [reduced NADPH-hemoprotein reductase] + O2 = lutein + [oxidized NADPH-hemoprotein reductase] + H2O
For diagram of reaction click here
Other name(s): CYP97C1; LUT1; CYP97C; carotene ε-monooxygenase
Systematic name: α-carotene,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)
Comments: A P-450 (heme-thiolate) protein.
References:
1. Pogson, B., McDonald, K.A., Truong, M., Britton, G. and DellaPenna, D. Arabidopsis carotenoid mutants demonstrate that lutein is not essential for photosynthesis in higher plants. Plant Cell 8 (1996) 1627-1639. [PMID: 8837513]
2. Tian, L., Musetti, V., Kim, J., Magallanes-Lundback, M. and DellaPenna, D. The Arabidopsis LUT1 locus encodes a member of the cytochrome P450 family that is required for carotenoid ε-ring hydroxylation activity. Proc. Natl. Acad. Sci. USA 101 (2004) 402-407. [PMID: 14709673]
3. Stigliani, A.L., Giorio, G. and D'Ambrosio, C. Characterization of P450 carotenoid β- and ε-hydroxylases of tomato and transcriptional regulation of xanthophyll biosynthesis in root, leaf, petal and fruit. Plant Cell Physiol 52 (2011) 851-865. [PMID: 21450689]
4. Chang, S., Berman, J., Sheng, Y., Wang, Y., Capell, T., Shi, L., Ni, X., Sandmann, G., Christou, P. and Zhu, C. Cloning and functional characterization of the maize (Zea mays L.) Carotenoid Epsilon Hydroxylase Gene. PLoS One 10 (2015) e0128758. [PMID: 26030746]
5. Reddy, C.S., Lee, S.H., Yoon, J.S., Kim, J.K., Lee, S.W., Hur, M., Koo, S.C., Meilan, J., Lee, W.M., Jang, J.K., Hur, Y., Park, S.U. and Kim, A.YB. Molecular cloning and characterization of carotenoid pathway genes and carotenoid content in Ixeris dentata var. albiflora. Molecules 22 (2017) . [PMID: 28858245]
Accepted name: (+)-piperitol/(+)-sesamin synthase
Reaction: (1) (+)-pinoresinol + [reduced NADPH-hemoprotein reductase]l + O2 = (+)-piperitol + [oxidized NADPH-hemoprotein reductase] + 2 H2O
(2) (+)-piperitol + [reduced NADPH-hemoprotein reductase] + O2 = (+)-sesamin + [oxidized NADPH-hemoprotein reductase] + 2 H2O
For diagram of reaction click here.
Other name(s): CYP81Q1; CYP81Q2; PS; PSS; SS; piperitol synthase; sesamin synthase
Systematic name: (+)-pinoresinol,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (cyclizing)
Comments: A cytochrome P-450 (heme-thiolate) protein. Isolated from Sesamum indicum (sesame) and S. radiatum (black sesame).
References:
1. Ono, E., Nakai, M., Fukui, Y., Tomimori, N., Fukuchi-Mizutani, M., Saito, M., Satake, H., Tanaka, T., Katsuta, M., Umezawa, T. and Tanaka, Y. Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin. Proc. Natl Acad. Sci. USA 103 (2006) 10116-10121. [PMID: 16785429]
Accepted name: hapalindole-type alkaloid chlorinase
Reaction: (1) hapalindole U + 2-oxoglutarate + O2 + chloride = hapalindole G + succinate + CO2 + H2O
(2)12-epi-fischerindole U + 2-oxoglutarate + O2 + chloride = 12-epi-fischerindole G + succinate + CO2 + H2O
For diagram of reaction click here.
Glossary: 12-epi-fischerindole U = (6aS,9S,10R,10aS)-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole
12-epi-fischerindole G = (6aR,8R,9S,10R,10aS)-8-chloro-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole
Other name(s): ambO5 (gene name); welO5 (gene name)
Systematic name: 12-epi-fischerindole U,2-oxoglutarate:oxygen oxidoreductase (13-halogenating)
Comments: The enzyme, characterized from hapalindole-type alkaloids-producing cyanobacteria, is a specialized Fe(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrates in a reaction that requires oxygen, chloride ions, ferrous iron and 2-oxoglutarate.
References:
1. Hillwig, M.L. and Liu, X. A new family of iron-dependent halogenases acts on freestanding substrates. Nat. Chem. Biol. 10 (2014) 921-923. [PMID: 25218740]
2. Zhu, Q., Hillwig, M.L., Doi, Y. and Liu, X. Aliphatic halogenase enables late-stage C-H functionalization: selective synthesis of a brominated fischerindole alkaloid with enhanced antibacterial activity. Chembiochem 17 (2016) 466-470. [PMID: 26749394]
3. Hillwig, M.L., Zhu, Q., Ittiamornkul, K. and Liu, X. Discovery of a promiscuous non-heme iron halogenase in ambiguine alkaloid biogenesis: implication for an evolvable enzyme family for late-stage halogenation of aliphatic carbons in small molecules. Angew Chem Int Ed Engl 55 (2016) 5780-5784. [PMID: 27027281]
Accepted name: L-threonyl-[L-threonyl-carrier protein] 4-chlorinase
Reaction: an L-threonyl-[L-threonyl-carrier protein] + 2-oxoglutarate + O2 + Cl- = a 4-chloro-L-threonyl-[L-threonyl-carrier protein] + succinate + CO2 + H2O
Other name(s): syrB2 (gene name)
Systematic name: L-threonyl-[L-threonyl-carrier protein],2-oxoglutarate:oxygen oxidoreductase (4-halogenating)
Comments: The enzyme, characterized from the bacterium Pseudomonas syringae, participates in syringomycin E biosynthesis. The enzyme is a specialized Fe(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrate in a reaction that requires oxygen, chloride ions, ferrous iron and 2-oxoglutarate.
References:
1. Vaillancourt, F.H., Yin, J. and Walsh, C.T. SyrB2 in syringomycin E biosynthesis is a nonheme FeII α-ketoglutarate- and O2-dependent halogenase. Proc. Natl Acad. Sci. USA 102 (2005) 10111-10116. [PMID: 16002467]
[EC 1.14.99.45 Transferred entry: carotene ε-monooxygenase. Now EC 1.14.14.158, carotene ε-monooxygenase (EC 1.14.99.45 created 2011, deleted 2018)]
Accepted name: cyclooctat-9-en-7-ol 5-monooxygenase
Reaction: cyclooctat-9-en-7-ol + reduced acceptor + O2 = cyclooctat-9-ene-5,7-diol + acceptor + H2O
For diagram of reaction click here.
Glossary: cyclooctat-9-en-7-ol = (1S,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulen-4-ol
cyclooctat-9-ene-5,7-diol = (1S,3R,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol
Other name(s): CotB3
Systematic name: cyclooctat-9-en-7-ol,hydrogen-donor:oxygen oxidoreductase (5-hydroxylating)
Comments: Isolated from the bacterium Streptomyces melanosporofaciens M1614-43f2. Involved in the biosynthesis of cyclooctatin.
References:
1. Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736-743. [PMID: 19635410]
2. Gorner, C., Schrepfer, P., Redai, V., Wallrapp, F., Loll, B., Eisenreich, W., Haslbeck, M. and Bruck, T. Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb. Cell Fact. 15 (2016) 86. [PMID: 27216162]
Accepted name: cyclooctatin synthase
Reaction: cyclooctat-9-ene-5,7-diol + reduced acceptor + O2 = cyclooctatin + acceptor + H2O
For diagram of reaction click here.
Glossary: cyclooctat-9-ene-5,7-diol = (1S,3R,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol
cyclooctatin = cycloctat-9-ene-5,7,18-triol = (1R,3R,3aS,4R,7S,9aS,10aS)-1-(hydroxymethyl-)4,9a-dimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol
Other name(s): CotB4
Systematic name: cyclooctat-9-ene-5,7-diol,hydrogen-donor:oxygen oxidoreductase (18-hydroxylating)
Comments: Isolated from the bacterium Streptomyces melanosporofaciens M1614-43f2.
References:
1. Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736-743. [PMID: 19635410]
2. Gorner, C., Schrepfer, P., Redai, V., Wallrapp, F., Loll, B., Eisenreich, W., Haslbeck, M. and Bruck, T. Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb. Cell Fact. 15 (2016) 86. [PMID: 27216162]
Accepted name: β-carotene 4-ketolase
Reaction: (1) β-carotene + 2 reduced acceptor + 2 O2 = echinenone + 2 acceptor + 3 H2O
(2) echinenone + 2 reduced acceptor + 2 O2 = canthaxanthin + 2 acceptor + 3 H2O
For diagram of reaction click here.
Glossary: echinenone = β,β-caroten-4-one
canthaxanthin = β,β-carotene-4,4′-dione
zeaxanthin = β,β-carotene-3,3′-diol
astaxanthin = 3,3′-dihydroxy-β,β-carotene-4,4′-dione
Other name(s): BKT (ambiguous); β-C-4 oxygenase; β-carotene ketolase; crtS (gene name); crtW (gene name)
Systematic name: β-carotene,donor:oxygen oxidoreductase (echinenone-forming)
Comments: The enzyme, studied from algae, plants, fungi, and bacteria, adds an oxo group at position 4 of a carotenoid β ring. It is involved in the biosynthesis of carotenoids such as astaxanthin and flexixanthin. The enzyme does not act on β rings that are hydroxylated at position 3, such as in zeaxanthin (cf. EC 1.14.99.64, zeaxanthin 4-ketolase). The enzyme from the yeast Xanthophyllomyces dendrorhous is bifuntional and also catalyses the activity of EC 1.14.15.24, β-carotene 3-hydroxylase.
References:
1. Lotan, T. and Hirschberg, J. Cloning and expression in Escherichia coli of the gene encoding β-C-4-oxygenase, that converts β-carotene to the ketocarotenoid canthaxanthin in Haematococcus pluvialis. FEBS Lett. 364 (1995) 125-128. [PMID: 7750556]
2. Breitenbach, J., Misawa, N., Kajiwara, S. and Sandmann, G. Expression in Escherichia coli and properties of the carotene ketolase from Haematococcus pluvialis. FEMS Microbiol. Lett. 140 (1996) 241-246. [PMID: 8764486]
3. Steiger, S. and Sandmann, G. Cloning of two carotenoid ketolase genes from Nostoc punctiforme for the heterologous production of canthaxanthin and astaxanthin. Biotechnol. Lett. 26 (2004) 813-817. [PMID: 15269553]
4. Ojima, K., Breitenbach, J., Visser, H., Setoguchi, Y., Tabata, K., Hoshino, T., van den Berg, J. and Sandmann, G. Cloning of the astaxanthin synthase gene from Xanthophyllomyces dendrorhous (Phaffia rhodozyma) and its assignment as a β-carotene 3-hydroxylase/4-ketolase. Mol. Genet. Genomics 275 (2006) 148-158. [PMID: 16416328]
5. Tao, L., Yao, H., Kasai, H., Misawa, N. and Cheng, Q. A carotenoid synthesis gene cluster from Algoriphagus sp. KK10202C with a novel fusion-type lycopene β-cyclase gene. Mol. Genet. Genomics 276 (2006) 79-86. [PMID: 16625353]
6. Kathiresan, S., Chandrashekar, A., Ravishankar, G.A. and Sarada, R. Regulation of astaxanthin and its intermediates through cloning and genetic transformation of β-carotene ketolase in Haematococcus pluvialis. J. Biotechnol. 196-197 (2015) 33-41. [PMID: 25612872]
Accepted name: zeaxanthin 4-ketolase
Reaction: (1) zeaxanthin + 2 reduced acceptor + 2 O2 = adonixanthin + 2 acceptor + 3 H2O
(2) adonixanthin + 2 reduced acceptor + 2 O2 = (3S,3′S)-astaxanthin + 2 acceptor + 3 H2O
For diagram of reaction click here.
Glossary: zeaxanthin = β,β-carotene-3,3′-diol
adonixanthin = 3,3′-dihydroxy-β,β-carotene-4-one
(3S,3′S)-astaxanthin = (3S,3′S)-3,3′-dihydroxy-β,β-carotene-4,4′-dione
Other name(s): BKT (ambiguous); crtW148 (gene name)
Systematic name: zeaxanthin,donor:oxygen oxidoreductase (adonixanthin-forming)
Comments: The enzyme has a similar activity to that of EC 1.14.99.63, β-carotene 4-ketolase, but unlike that enzyme is able to also act on zeaxanthin.
References:
1. Zhong, Y.J., Huang, J.C., Liu, J., Li, Y., Jiang, Y., Xu, Z.F., Sandmann, G. and Chen, F. Functional characterization of various algal carotenoid ketolases reveals that ketolating zeaxanthin efficiently is essential for high production of astaxanthin in transgenic Arabidopsis. J. Exp. Bot. 62 (2011) 3659-3669. [PMID: 21398427]
2. Huang, J., Zhong, Y., Sandmann, G., Liu, J. and Chen, F. Cloning and selection of carotenoid ketolase genes for the engineering of high-yield astaxanthin in plants. Planta 236 (2012) 691-699. [PMID: 22526507]
[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)]
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.
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: toxoflavin synthase
Reaction: (1) S-adenosyl-L-methionine + 1,6-didemethyltoxoflavin = S-adenosyl-L-homocysteine + reumycin
(2) S-adenosyl-L-methionine + reumycin = S-adenosyl-L-homocysteine + toxoflavin
For diagram of reaction click here.
Glossary: reumycin = 1-demethyltoxoflavin
toxoflavin = 1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
Other name(s): toxA (gene name)
Systematic name: S-adenosyl-L-methionine:1,6-didemethyltoxoflavin N1,N6-dimethyltransferase (toxoflavin-forming)
Comments: The enzyme is a dual-specificity methyltransferase that catalyses the last two steps of toxoflavin biosynthesis. Toxoflavin is a major virulence factor of several bacterial crop pathogens.
References:
1. Fenwick, M.K., Philmus, B., Begley, T.P. and Ealick, S.E. Burkholderia glumae ToxA Is a dual-specificity methyltransferase that catalyzes the last two steps of toxoflavin biosynthesis. Biochemistry 55 (2016) 2748-2759. [PMID: 27070241]
Accepted name: diglucosylglycerate octanoyltransferase
Reaction: octanoyl-CoA + 2-O-[α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate. = 2-O-[6-O-octanoyl-α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate. + CoA
Other name(s): octT (gene name); DGG octanoyltransferase
Systematic name: octanoyl-CoA:2-O-[α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate octanoyltransferase
Comments: The enzyme, characterized from mycobacteria, is involved in the biosynthesis of methylglucose lipopolysaccharide (MGLP). The enzyme can also act on 2-O-(α-D-glucopyranosyl)-D-glycerate, but with lower activity.
References:
1. Maranha, A., Moynihan, P.J., Miranda, V., Correia Lourenco, E., Nunes-Costa, D., Fraga, J.S., Jose Barbosa Pereira, P., Macedo-Ribeiro, S., Ventura, M.R., Clarke, A.J. and Empadinhas, N. Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides. Sci Rep 5 (2015) 13610. [PMID: 26324178]
Accepted name: acylphloroglucinol glucosyltransferase
Reaction: UDP-α-D-glucose + 2-acylphloroglucinol = UDP + 2-acylphloroglucinol 1-O-β-D-glucoside
For diagram of reaction click here.
Glossary: phlorisobutyrophenone = 2-methyl-1-(2,4,6-trihydroxyphenyl)propan-1-one
phlorisovalerophenone = 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one
Other name(s): UGT71K3
Systematic name: UDP-α-D-glucose:2-acylphloroglucinol 1-O-β-glucosyltransferase
Comments: Isolated from strawberries (Fragaria × ananassa). Acts best on phloroisovalerophenone and phlorobutyrophenone but will also glycosylate many other phenolic compounds. A minor product of the reaction is the 5-O-β-D-glucoside
References:
1. Song, C., Zhao, S., Hong, X., Liu, J., Schulenburg, K. and Schwab, W. A UDP-glucosyltransferase functions in both acylphloroglucinol glucoside and anthocyanin biosynthesis in strawberry (Fragaria × ananassa). Plant J. 85 (2016) 730-742. [PMID: 26859691]
Accepted name: corrinoid adenosyltransferase
Reaction: (1) 2 ATP + 2 cob(II)alamin + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(III)alamin + an oxidized flavoprotein
(1a) 2 cob(II)alamin + 2 [corrinoid adenosyltransferase] = 2 [corrinoid adenosyltransferase]-cob(II)alamin
(1b) a reduced flavoprotein + 2 [corrinoid adenosyltransferase]-cob(II)alamin = an oxidized flavoprotein + 2 [corrinoid adenosyltransferase]-cob(I)alamin (spontaneous)
(1c) 2 ATP + 2 [corrinoid adenosyltransferase]-cob(I)alamin = 2 triphosphate + 2 adenosylcob(III)alamin + 2 [corrinoid adenosyltransferase]
(2) 2 ATP + 2 cob(II)yrinic acid a,c-diamide + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(III)yrinic acid a,c-diamide + an oxidized flavoprotein
(2a) 2 cob(II)yrinic acid a,c-diamide + 2 [corrinoid adenosyltransferase] = 2 [corrinoid adenosyltransferase]-cob(II)yrinic acid a,c-diamide
(2b) a reduced flavoprotein + 2 [corrinoid adenosyltransferase]-cob(II)yrinic acid a,c-diamide = an oxidized flavoprotein + 2 [corrinoid adenosyltransferase]-cob(I)yrinic acid a,c-diamide (spontaneous)
(2c) 2 ATP + 2 [corrinoid adenosyltransferase]-cob(I)yrinic acid a,c-diamide = 2 triphosphate + 2 adenosylcob(III)yrinic acid a,c-diamide + 2 [corrinoid adenosyltransferase]
For diagram of reaction, click here or click here
Other name(s): MMAB (gene name); cobA (gene name); cobO (gene name); pduO (gene name); ATP:corrinoid adenosyltransferase; cob(I)alamin adenosyltransferase; aquacob(I)alamin adenosyltransferase; aquocob(I)alamin vitamin B12s adenosyltransferase; ATP:cob(I)alamin Coβ-adenosyltransferase; ATP:cob(I)yrinic acid-a,c-diamide Coβ-adenosyltransferase; cob(I)yrinic acid a,c-diamide adenosyltransferase
Systematic name: ATP:cob(II)alamin Coβ-adenosyltransferase
Comments: The corrinoid adenosylation pathway comprises three steps: (i) reduction of Co(III) within the corrinoid to Co(II) by a one-electron transfer. This can occur non-enzymically in the presence of dihydroflavin nucleotides or reduced flavoproteins [3]. (ii) Co(II) is bound by corrinoid adenosyltransferase, resulting in displacement of the lower axial ligand by an aromatic residue. The reduction potential of the 4-coordinate Co(II) intermediate is raised by ~250 mV compared with the free compound, bringing it to within physiological range. This is followed by a second single-electron transfer from either free dihydroflavins or the reduced flavin cofactor of flavoproteins, resulting in reduction to Co(I) [7]. (iii) the Co(I) conducts a nucleophilic attack on the adenosyl moiety of ATP, resulting in transfer of the deoxyadenosyl group and oxidation of the cobalt atom to Co(III) state. Three types of corrinoid adenosyltransferases, not related by sequence, have been described. In the anaerobic bacterium Salmonella enterica they are encoded by the cobA gene (a housekeeping enzyme involved in both the de novo biosynthesis and the salvage of adenosylcobalamin), the pduO gene (involved in (S)-propane-1,2-diol utilization), and the eutT gene (involved in ethanolamine utilization). Since EutT hydrolyses triphosphate to diphosphate and phosphate during catalysis, it is classified as a separate enzyme. The mammalian enzyme belongs to the PduO type. The enzyme can act on other corrinoids, such as cob(II)inamide.
Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, PDB, CAS registry number: 37277-84-2
References:
1. Vitols, E., Walker, G.A. and Huennekens, F.M. Enzymatic conversion of vitamin B12s to a cobamide coenzyme, α-(5,6-dimethylbenzimidazolyl)deoxyadenosylcobamide (adenosyl-B12). J. Biol. Chem. 241 (1966) 1455-1461. [PMID: 5946606]
2. Bauer, C.B., Fonseca, M.V., Holden, H.M., Thoden, J.B., Thompson, T.B., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP. Biochemistry 40 (2001) 361-374. [PMID: 11148030]
3. Fonseca, M.V. and Escalante-Semerena, J.C. Reduction of Cob(III)alamin to Cob(II)alamin in Salmonella enterica serovar typhimurium LT2. J. Bacteriol. 182 (2000) 4304-4309. [PMID: 10894741]
4. Fonseca, M.V. and Escalante-Semerena, J.C. An in vitro reducing system for the enzymic conversion of cobalamin to adenosylcobalamin. J. Biol. Chem. 276 (2001) 32101-32108. [PMID: 11408479]
5. Suh, S. and Escalante-Semerena, J.C. Purification and initial characterization of the ATP:corrinoid adenosyltransferase encoded by the cobA gene of Salmonella typhimurium. J. Bacteriol. 177 (1995) 921-925. [PMID: 7860601]
6. Mera, P.E., St Maurice, M., Rayment, I. and Escalante-Semerena, J.C. Residue Phe112 of the human-type corrinoid adenosyltransferase (PduO) enzyme of Lactobacillus reuteri is critical to the formation of the four-coordinate Co(II) corrinoid substrate and to the activity of the enzyme. Biochemistry 48 (2009) 3138-3145. [PMID: 19236001]
7. Mera, P.E. and Escalante-Semerena, J.C. Dihydroflavin-driven adenosylation of 4-coordinate Co(II) corrinoids: are cobalamin reductases enzymes or electron transfer proteins. J. Biol. Chem. 285 (2010) 2911-2917. [PMID: 19933577]
[EC 2.5.1.77 Transferred entry: 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase. Now EC 2.5.1.147, 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-methylphenol transferase and EC 4.3.1.32, 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase. (EC 2.5.1.77 created 2010, deleted 2017)]
Accepted name: 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-hydroxyphenyl transferase
Reaction: 5-amino-6-(D-ribitylamino)uracil + L-tyrosine + S-adenosyl-L-methionine = 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil + 2-iminoacetate + L-methionine + 5′-deoxyadenosine
For diagram of reaction click here.
Glossary: 5-amino-6-(D-ribitylamino)uracil = 5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione
Other name(s): cofH (gene name); cbiF (gene name) (ambiguous)
Systematic name: 5-amino-6-(D-ribitylamino)uracil:L-tyrosine, 4-hydroxyphenyl transferase
Comments: The enzyme is involved in the production of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (Fo), the precursor of the redox cofactor coenzyme F420, which is found in methanogens and in various actinobacteria. Fo is also produced by some cyanobacteria and eukaryotes. The enzyme, which forms a complex with EC 4.3.1.32, 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase, is a radical SAM enzyme that uses the 5′-deoxyadenosyl radical to initiate the reaction.
References:
1. Decamps, L., Philmus, B., Benjdia, A., White, R., Begley, T.P. and Berteau, O. Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. J. Am. Chem. Soc. 134 (2012) 18173-18176. [PMID: 23072415]
2. Philmus, B., Decamps, L., Berteau, O. and Begley, T.P. Biosynthetic versatility and coordinated action of 5′-deoxyadenosyl radicals in deazaflavin biosynthesis. J. Am. Chem. Soc. 137 (2015) 5406-5413. [PMID: 25781338]
Accepted name: carbamate kinase
Reaction: ATP + NH3 + hydrogencarbonate = ADP + carbamoyl phosphate + H2O (overall reaction)
(1a) ATP + carbamate = ADP + carbamoyl phosphate
(1b) NH3 + hydrogencarbonate = carbamate + H2O (spontaneous)
For diagram of reaction click here
Other name(s): CKase; carbamoyl phosphokinase; carbamyl phosphokinase
Systematic name: ATP:carbamate phosphotransferase
Comments: The enzyme catalyses the reversible conversion of carbamoyl phosphate and ADP to ATP and carbamate, which hydrolyses to ammonia and hydrogencarbonate. The physiological role of the enzyme is to generate ATP.
Links to other databases: BRENDA, EXPASY, ExplorEnz, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9026-69-1
References:
1. Jones, M.E., Spector, L. and Lipmann, F. Carbamyl phosphate, the carbamyl donor in enzymatic citrulline synthesis. J. Am. Chem. Soc. 77 (1955) 819-820.
2. Davis, R.H. Carbamyl phosphate synthesis in Neurospora crassa. I. Preliminary characterization of arginine-specific carbamyl phosphokinase. Biochim. Biophys. Acta 107 (1965) 44-53. [PMID: 5857367]
3. Glasziou, K.T. The metabolism of arginine in Serratia marcescens. II. Carbamyladenosine diphosphate phosphoferase. Aust. J. Biol. Sci. 9 (1956) 253-262.
4. Bishop, S.H. and Grisolia, S. Crystalline carbamate kinase. Biochim. Biophys. Acta 118 (1966) 211-215. [PMID: 4959296]
5. Srivenugopal, K.S. and Adiga, P.R. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J. Biol. Chem. 256 (1981) 9532-9541. [PMID: 6895223]
Accepted name: L-cysteine S-thiosulfotransferase
Reaction: (1) [SoxY protein]-L-cysteine + thiosulfate + 2 ferricytochrome c = [SoxY protein]-S-sulfosulfanyl-L-cysteine + 2 ferrocytochrome c + 2H+
(2) [SoxY protein]-S-sulfanyl-L-cysteine + thiosulfate + 2 ferricytochrome c = [SoxY protein]-S-(2-sulfodisulfanyl)-L-cysteine + 2 ferrocytochrome c + 2H+
Other name(s): SoxXA
Systematic name: thiosulfate:[SoxY protein]-L-cysteine thiosufotransferase
Comments: The enzyme is part of the Sox enzyme system, which participates in a bacterial thiosulfate oxidation pathway that produces sulfate. It catalyses two reactions in the pathway - early in the pathway it attaches a thiosulfate molecule to the sulfur atom of an L-cysteine of a SoxY protein; later it transfers a second thiosulfate molecule to a sulfane group that is already attached to the same cysteine residue.
References:
1. Friedrich, C.G., Quentmeier, A., Bardischewsky, F., Rother, D., Kraft, R., Kostka, S. and Prinz, H. Novel genes coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus GB17. J. Bacteriol. 182 (2000) 4677-4687. [PMID: 10940005]
2. Cheesman, M.R., Little, P.J. and Berks, B.C. Novel heme ligation in a c-type cytochrome involved in thiosulfate oxidation: EPR and MCD of SoxAX from Rhodovulum sulfidophilum. Biochemistry 40 (2001) 10562-10569. [PMID: 11523998]
3. Rother, D. and Friedrich, C.G. The cytochrome complex SoxXA of Paracoccus pantotrophus is produced in Escherichia coli and functional in the reconstituted sulfur-oxidizing enzyme system. Biochim. Biophys. Acta 1598 (2002) 65-73. [PMID: 12147345]
4. Bamford, V.A., Bruno, S., Rasmussen, T., Appia-Ayme, C., Cheesman, M.R., Berks, B.C. and Hemmings, A.M. Structural basis for the oxidation of thiosulfate by a sulfur cycle enzyme. EMBO J. 21 (2002) 5599-5610. [PMID: 12411478]
5. Dambe, T., Quentmeier, A., Rother, D., Friedrich, C. and Scheidig, A.J. Structure of the cytochrome complex SoxXA of Paracoccus pantotrophus, a heme enzyme initiating chemotrophic sulfur oxidation. J. Struct. Biol. 152 (2005) 229-234. [PMID: 16297640]
6. Hensen, D., Sperling, D., Truper, H.G., Brune, D.C. and Dahl, C. Thiosulphate oxidation in the phototrophic sulphur bacterium Allochromatium vinosum. Mol. Microbiol. 62 (2006) 794-810. [PMID: 16995898]
7. Grabarczyk, D.B. and Berks, B.C. Intermediates in the Sox sulfur oxidation pathway are bound to a sulfane conjugate of the carrier protein SoxYZ. PLoS One 12 (2017) e0173395. [PMID: 28257465]
Accepted name: folate γ-glutamyl hydrolase
Reaction: tetrahydropteroyl-(γ-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate
For diagram of reaction click here.
Other name(s): GGH (gene name) conjugase; folate conjugase; lysosomal γ-glutamyl carboxypeptidase; γ-Glu-X carboxypeptidase; pteroyl-poly-γ-glutamate hydrolase; carboxypeptidase G; folic acid conjugase; poly(γ-glutamic acid) endohydrolase; polyglutamate hydrolase; poly(glutamic acid) hydrolase II; pteroylpoly-γ-glutamyl hydrolase; γ-glutamyl hydrolase
Systematic name: tetrahydropteroyl-poly-γ-glutamyl γ-glutamyl hydrolase
Comments: The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-γ-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH2 from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants.
Links to other databases: BRENDA, EXPASY, ExplorEnz, GTD, KEGG, MetaCyc, MEROPS, PDB, CAS registry number: 9074-87-7
References:
1. McGuire, J.J. and Coward, J.K. Pteroylpolyglutamates: biosynthesis, degradation and function.. In: Blakley, R.L. and Benkovic, S.J. (Eds), Folates and Pterins, John Wiley and Sons, New York, 1984, pp. 135-191.
2. Wang, Y., Nimec, Z., Ryan, T.J., Dias, J.A. and Galivan, J. The properties of the secreted γ-glutamyl hydrolases from H35 hepatoma cells. Biochim. Biophys. Acta 1164 (1993) 227-235. [PMID: 8343522]
3. Yao, R., Rhee, M.S. and Galivan, J. Effects of γ-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells. Mol. Pharmacol. 48 (1995) 505-511. [PMID: 7565632]
4. Yao, R., Schneider, E., Ryan, T.J. and Galivan, J. Human γ-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. Proc. Natl. Acad. Sci. USA 93 (1996) 10134-10138. [PMID: 8816764]
5. Yao, R., Nimec, Z., Ryan, T.J. and Galivan, J. Identification, cloning, and sequencing of a cDNA coding for rat γ-glutamyl hydrolase. J. Biol. Chem. 271 (1996) 8525-8528. [PMID: 8621474]
6. Orsomando, G., de la Garza, R.D., Green, B.J., Peng, M., Rea, P.A., Ryan, T.J., Gregory, J.F., 3rd and Hanson, A.D. Plant γ-glutamyl hydrolases and folate polyglutamates: characterization, compartmentation, and co-occurrence in vacuoles. J. Biol. Chem. 280 (2005) 28877-28884. [PMID: 15961386]
7. Akhtar, T.A., McQuinn, R.P., Naponelli, V., Gregory, J.F., 3rd, Giovannoni, J.J. and Hanson, A.D. Tomato γ-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation. Plant Physiol. 148 (2008) 775-785. [PMID: 18757550]
[EC 3.6.3.1 Transferred entry: phospholipid-translocating ATPase. Now EC 7.6.2.1, P-type phospholipid transporter (EC 3.6.3.1 created 2000 (EC 3.6.3.13 created 2000, incorporated 2001), deleted 2018)]
[EC 3.6.3.6 Transferred entry: H+-exporting ATPase. Now EC 7.1.2.1, H+-exporting ATPase (EC 3.6.3.6 created 1984 as EC 3.6.1.35, transferred 2000 to EC 3.6.3.6, deleted 2018)]
[EC 3.6.3.7 Transferred entry: Na+-exporting ATPase. Now EC 7.2.2.3, P-type Na+ transporter (EC 3.6.3.7 created 2000, modified 2001, transferred 2018 to EC 7.2.2.3, deleted 2018)]
[EC 3.6.3.14 Transferred entry: H+-transporting two-sector ATPase. Now EC 7.1.2.2, H+-transporting two-sector ATPase (EC 3.6.3.14 created 1984 as EC 3.6.1.34, transferred 2000 to EC 3.6.3.14, deleted 2018)]
[EC 3.6.3.15 Transferred entry: Na+-transporting two-sector ATPase. Now EC 7.2.2.1, Na+-transporting two-sector ATPase (EC 3.6.3.15 created 2000, transferred 2018 to EC 7.2.2.1, deleted 2018)]
[EC 3.6.3.18 Transferred entry: oligosaccharide-transporting ATPase. Now EC 7.5.2.2, oligosaccharide-transporting ATPase (EC 3.6.3.18 created 2000, deleted 2018)]
[EC 3.6.3.19 Transferred entry: maltose-transporting ATPase. Now EC 7.5.2.1, maltose-transporting ATPase (EC 3.6.3.19 created 2000, deleted 2018)]
[EC 3.6.3.21 Transferred entry: polar-amino-acid-transporting ATPase. Now EC 7.4.2.1, polar-amino-acid-transporting ATPase (EC 3.6.3.21 created 2000, deleted 2018)]
[EC 3.6.3.22 Transferred entry: nonpolar-amino-acid-transporting ATPase. Now EC 7.4.2.2, nonpolar-amino-acid-transporting ATPase (EC 3.6.3.22 created 2000, deleted 2018)]
[EC 3.6.3.27 Transferred entry: phosphate-transporting ATPase. Now EC 7.3.2.1, phosphate-transporting ATPase (EC 3.6.3.27 created 2000, deleted 2018)]
[EC 3.6.3.28 Transferred entry: phosphonate-transporting ATPase. Now EC 7.3.2.2, phosphonate-transporting ATPase (EC 3.6.3.28 created 2000, deleted 2018)]
[EC 3.6.3.44 Transferred entry: xenobiotic-transporting ATPase. Now EC 7.6.2.2, xenobiotic-transporting ATPase (EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006, deleted 2018)]
[EC 3.6.3.46 Transferred entry: cadmium-transporting ATPase. Now EC 7.2.2.2, cadmium-transporting ATPase (EC 3.6.3.46 created 2000, transferred 2018 to EC 7.2.2.2, deleted 2018)]
[EC 3.6.4.3 Transferred entry: microtubule-severing ATPase. Now EC 5.6.1.1, microtubule-severing ATPase (EC 3.6.4.3 created 2000 as 3.6.4.3, deleted 2018)]
[EC 3.6.4.11 Deleted entry: nucleoplasmin ATPase. The activity has been shown not to take place. (EC 3.6.4.11 created 2000, deleted 2018)]
[EC 4.1.1.3 Transferred entry: oxaloacetate decarboxylase. Now recognized to be two enzymes EC 7.2.4.2 [oxaloacetate decarboxylase (Na+ extruding)] and EC 4.1.1.112 (oxaloacetate decarboxylase). (EC 4.1.1.3 created 1961 as EC 4.1.1.3, modified 1986, modified 2000, deleted 2018)]
[EC 4.1.1.41 Transferred entry: (S)-methylmalonyl-CoA decarboxylase. Now EC 7.2.4.3, (S)-methylmalonyl-CoA decarboxylase (EC 4.1.1.41 created 1972, modified 1983, modified 1986, deleted 2018)]
Accepted name: phosphomevalonate decarboxylase
Reaction: ATP + (R)-5-phosphomevalonate = ADP + phosphate + isopentenyl phosphate + CO2
For diagram of reaction click here
Systematic name: ATP:(R)-5-phosphomevalonate carboxy-lyase (adding ATP; isopentenyl-phosphate-forming)
Comments: The enzyme participates in a mevalonate pathway that occurs in archaea other than the extreme acidophiles of the Thermoplasmatales order. cf. EC 4.1.1.110, bisphosphomevalonate decarboxylase
Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, CAS registry number:
References:
1. Vannice, J.C., Skaff, D.A., Keightley, A., Addo, J.K., Wyckoff, G.J. and Miziorko, H.M. Identification in Haloferax volcanii of phosphomevalonate decarboxylase and isopentenyl phosphate kinase as catalysts of the terminal enzyme reactions in an archaeal alternate mevalonate pathway. J. Bacteriol. 196 (2014) 1055-1063. [PMID: 24375100]
Accepted name: oxaloacetate decarboxylase
Reaction: oxaloacetate = pyruvate + CO2
Other name(s): oxaloacetate β-decarboxylase; oxalacetic acid decarboxylase; oxalate β-decarboxylase; oxaloacetate carboxy-lyase
Systematic name: oxaloacetate carboxy-lyase (pyruvate-forming)
Comments: Requires a divalent metal cation. The enzymes from the fish Gadus morhua (Atlantic code) and the bacterium Micrococcus luteus prefer Mn2+, while those from the bacteria Pseudomonas putida and Pseudomonas aeruginosa prefer Mg2+. Unlike EC 7.2.4.2 [oxaloacetate decarboxylase (Na+ extruding)], there is no evidence of the enzyme’s involvement in Na+ transport.
References:
1. Schmitt, A., Bottke, I. and Siebert, G. Eigenschaften einer Oxaloacetat-Decarboxylase aus Dorschmuskulatur. Hoppe-Seyler's Z. Physiol. Chem. 347 (1966) 18-34. [PMID: 5972993]
2. Herbert, D. Oxalacetic carboxylase of Micrococcus lysodeikticus. Methods Enzymol. 1 (1955) 753-757.
3. Horton, A.A. and Kornberg, H.L. Oxaloacetate 4-carboxy-lyase from Pseudomonas ovalis chester. Biochim. Biophys. Acta 89 (1964) 381-383. [PMID: 14205502]
4. Sender, P.D., Martin, M.G., Peiru, S. and Magni, C. Characterization of an oxaloacetate decarboxylase that belongs to the malic enzyme family. FEBS Lett. 570 (2004) 217-222. [PMID: 15251467]
5. Narayanan, B.C., Niu, W., Han, Y., Zou, J., Mariano, P.S., Dunaway-Mariano, D. and Herzberg, O. Structure and function of PA4872 from Pseudomonas aeruginosa, a novel class of oxaloacetate decarboxylase from the PEP mutase/isocitrate lyase superfamily. Biochemistry 47 (2008) 167-182. [PMID: 18081320]
Accepted name: L-tyrosine isonitrile synthase
Reaction: L-tyrosine + D-ribulose 5-phosphate = (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H2O
For diagram of reaction click here
Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate = L-tyrosine isonitrile
paerucumarin = 6,7-dihydroxy-3-isocyanochromen-2-one
rhabduscin = N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-{4-[(E)-2-isocyanoethenyl]phenoxy}-2-methyloxan-3-yl]acetamide
Other name(s): pvcA (gene name)
Systematic name: L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming)
Comments: The enzymes from the bacteria Pseudomonas aeruginosa and Xenorhabdus nematophila are involved in the biosynthesis of paerucumarin and rhabduscin, respectively. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tyrosine and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.25, L-tryptophan isonitrile synthase.
References:
1. Clarke-Pearson, M.F. and Brady, S.F. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J. Bacteriol. 190 (2008) 6927-6930. [PMID: 18689486]
2. Drake, E.J. and Gulick, A.M. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J. Mol. Biol. 384 (2008) 193-205. [PMID: 18824174]
3. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]
Accepted name: L-tryptophan isonitrile synthase
Reaction: L-tryptophan + D-ribulose 5-phosphate = (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H2O
For diagram of reaction click here (mechanism)
Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile
hydroxyacetone = 1-hydroxypropan-2-one
Other name(s): isnA (gene name); ambI1 (gene name); well1 (gene name)
Systematic name: L-tryptophan:D-ribulose-5-phosphate lyase (isonitrile-forming)
Comments: The enzymes from cyanobacteria that belong to the Nostocales order participate in the biosynthesis of hapalindole-type alkaloids. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tryptophan and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.24, L-tyrosine isonitrile synthase
References:
1. Brady, S.F. and Clardy, J. Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem Int Ed Engl 44 (2005) 7063-7065. [PMID: 16206308]
2. Brady, S.F. and Clardy, J. Systematic investigation of the Escherichia coli metabolome for the biosynthetic origin of an isocyanide carbon atom. Angew Chem Int Ed Engl 44 (2005) 7045-7048. [PMID: 16217820]
3. Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372-377. [PMID: 24180436]
4. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]
Accepted name: 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase
Reaction: 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil + S-adenosyl-L-methionine = 7,8-didemethyl-8-hydroxy-5-deazariboflavin + NH3 + L-methionine + 5′-deoxyadenosine
For diagram of reaction click here.
Glossary: 7,8-didemethyl-8-hydroxy-5-deazariboflavin = Fo
Other name(s): Fo synthase; fbiC (gene name) (ambiguous); cofG (gene name)
Systematic name: 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil ammonia-lyase (7,8-didemethyl-8-hydroxy-5-deazariboflavin-forming)
Comments: The enzyme produces the Fo precursor of the redox cofactor coenzyme F420, which is found in methanogens and in various actinobacteria. Fo is also produced by some cyanobacteria and eukaryotes. The enzyme, which forms a complex with EC 2.5.1.147, 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-hydroxyphenyl transferase, is a radical SAM enzyme that uses the 5′-deoxyadenosyl radical to catalyse the condensation reaction.
References:
1. Decamps, L., Philmus, B., Benjdia, A., White, R., Begley, T.P. and Berteau, O. Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. J. Am. Chem. Soc. 134 (2012) 18173-18176. [PMID: 23072415]
2. Philmus, B., Decamps, L., Berteau, O. and Begley, T.P. Biosynthetic versatility and coordinated action of 5′-deoxyadenosyl radicals in deazaflavin biosynthesis. J. Am. Chem. Soc. 137 (2015) 5406-5413. [PMID: 25781338]
Accepted name: imidazole glycerol-phosphate synthase
Reaction: (1) 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + L-glutamine = 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + NH3 = 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + H2O
For diagram of reaction click here.
Other name(s): IGP synthase; hisFH (gene names); HIS7 (gene name)
Systematic name: 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate-lyase (L-glutamine-hydrolysing; 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide-forming)
Comments: The enzyme is involved in histidine biosynthesis, as well as purine nucleotide biosynthesis. The enzymes from archaea and bacteria are heterodimeric. A glutaminase component (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 25 Å tunnel to a cyclase component, which adds it to the imidazole ring, leading to lysis of the molecule and cyclization of one of the products. The glutminase subunit is only active within the dimeric complex. In fungi and plants the two subunits are combined into a single polypeptide.
References:
1. Klem, T.J. and Davisson, V.J. Imidazole glycerol phosphate synthase: the glutamine amidotransferase in histidine biosynthesis. Biochemistry 32 (1993) 5177-5186. [PMID: 8494895]
2. Fujimori, K. and Ohta, D. An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant. FEBS Lett. 428 (1998) 229-234. [PMID: 9654139]
3. Beismann-Driemeyer, S. and Sterner, R. Imidazole glycerol phosphate synthase from Thermotoga maritima. Quaternary structure, steady-state kinetics, and reaction mechanism of the bienzyme complex. J. Biol. Chem 276 (2001) 20387-20396. [PMID: 11264293]
4. Douangamath, A., Walker, M., Beismann-Driemeyer, S., Vega-Fernandez, M.C., Sterner, R. and Wilmanns, M. Structural evidence for ammonia tunneling across the (β α)8 barrel of the imidazole glycerol phosphate synthase bienzyme complex. Structure 10 (2002) 185-193. [PMID: 11839304]
5. Chaudhuri, B.N., Lange, S.C., Myers, R.S., Davisson, V.J. and Smith, J.L. Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme. Biochemistry 42 (2003) 7003-7012. [PMID: 12795595]
[EC 4.3.99.2 Transferred entry: carboxybiotin decarboxylase. Now EC 7.2.4.1, carboxybiotin decarboxylase (EC 4.3.99.2 created 2008, deleted 2018)]
[EC 4.4.1.6 Transferred entry: S-alkylcysteine lyase. Now included in EC 4.4.1.13, cysteine-S-conjugate β-lyase (EC 4.4.1.6 created 1965, deleted 1972, reinstated 1976, deleted 2018)]
[EC 4.4.1.8 Transferred entry: cystathionine β-lyase. Now included in EC 4.4.1.13, cysteine-S-conjugate β-lyase (EC 4.4.1.8 created 1972, deleted 2018)]
EC 5.6 Isomerases altering macromolecular conformation
EC 5.6.1 Enzymes altering polypeptide conformation or assembly
Accepted name: microtubule-severing ATPase
Reaction: n ATP + n H2O + a microtubule = n ADP + n phosphate + (n+1) α/β tubulin heterodimers
Other name(s): katanin
Systematic name: ATP phosphohydrolase (tubulin-dimerizing)
Comments: A member of the AAA-ATPase family, active in splitting microtubules into tubulin dimers in the centrosome.
References:
1. McNally, F.J. and Vale, R.D. Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75 (1993) 419-429. [PMID: 8221885]
2. Hartman, J.J., Mahr, J., McNally, K., Okawa, K., Iwamatsu, A., Thomas, S., Cheesman, S., Heuser, J., Vale, R.D. and McNally, F.J. Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93 (1998) 277-287. [PMID: 9568719]
Accepted name: medium-chain acyl-CoA ligase
Reaction: ATP + a medium-chain fatty acid + CoA = AMP + diphosphate + a medium-chain acyl-CoA
Other name(s): fadK (gene name); lvaE (gene name); butyryl-CoA synthetase; fatty acid thiokinase (medium chain); acyl-activating enzyme; fatty acid elongase; fatty acid activating enzyme; fatty acyl coenzyme A synthetase; butyrate—CoA ligase; butyryl-coenzyme A synthetase; L-(+)-3-hydroxybutyryl CoA ligase; short-chain acyl-CoA synthetase; medium-chain acyl-CoA synthetase; butanoate:CoA ligase (AMP-forming)
Systematic name: medium-chain fatty acid:CoA ligase (AMP-forming)
Comments: Acts on fatty acids from C4 to C11 and on the corresponding 3-hydroxy and 2,3- or 3,4-unsaturated acids. The enzyme from the bacterium Pseudomonas putida also acts on 4-oxo and 4-hydroxy derivatives.
Links to other databases: BRENDA, EXPASY, ExplorEnz, GTD, , KEGG, MetaCyc, PDB, CAS registry number: 9080-51-7
References:
1. Mahler, H.R., Wakil, S.J. and Bock, R.M. Studies on fatty acid oxidation. I. Enzymatic activation of fatty acids. J. Biol. Chem. 204 (1953) 453-468. [PMID: 13084616]
2. Massaro, E.J. and Lennarz, W.J. The partial purification and characterization of a bacterial fatty acyl coenzyme A synthetase. Biochemistry 4 (1965) 85-90. [PMID: 14285249]
3. Websterlt, J.R., Gerowin, L.D. and Rakita, L. Purification and characteristics of a butyryl coenzyme A synthetase from bovine heart mitochondria. J. Biol. Chem. 240 (1965) 29-33. [PMID: 14253428]
4. Morgan-Kiss, R.M. and Cronan, J.E. The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated short chain acyl-CoA synthetase. J. Biol. Chem. 279 (2004) 37324-37333. [PMID: 15213221]
5. Rand, J.M., Pisithkul, T., Clark, R.L., Thiede, J.M., Mehrer, C.R., Agnew, D.E., Campbell, C.E., Markley, A.L., Price, M.N., Ray, J., Wetmore, K.M., Suh, Y., Arkin, A.P., Deutschbauer, A.M., Amador-Noguez, D. and Pfleger, B.F. A metabolic pathway for catabolizing levulinic acid in bacteria. Nat Microbiol 2 (2017) 1624-1634. [PMID: 28947739]
EC 7.1 Catalysing the translocation of hydrons
EC 7.1.1 Hydron translocation or charge separation linked to oxidoreductase reactions
Accepted name: proton-translocating NAD(P)+ transhydrogenase
Reaction: NADPH + NAD+ + H+[side 1] = NADP+ + NADH + H+[side 2]
Other name(s): pntA (gene name); pntB (gene name); NNT (gene name)
Systematic name: NADPH:NAD+ oxidoreductase (H+-transporting)
Comments: The enzyme is a membrane bound proton-translocating pyridine nucleotide transhydrogenase that couples the reversible reduction of NADP by NADH to an inward proton translocation across the membrane. In the bacterium Escherichia coli the enzyme provides a major source of cytosolic NADPH. Detoxification of reactive oxygen species in mitochondria by glutathione peroxidases depends on NADPH produced by this enzyme.
References:
1. Clarke, D.M. and Bragg, P.D. Cloning and expression of the transhydrogenase gene of Escherichia coli. J. Bacteriol. 162 (1985) 367-373. [PMID: 3884596]
2. Clarke, D.M. and Bragg, P.D. Purification and properties of reconstitutively active nicotinamide nucleotide transhydrogenase of Escherichia coli. Eur. J. Biochem. 149 (1985) 517-523. [PMID: 3891338]
3. Glavas, N.A., Hou, C. and Bragg, P.D. Involvement of histidine-91 of the β subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli. Biochemistry 34 (1995) 7694-7702. [PMID: 7779816]
4. Sauer, U., Canonaco, F., Heri, S., Perrenoud, A. and Fischer, E. The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 279 (2004) 6613-6619. [PMID: 14660605]
5. Bizouarn, T., Fjellstrom, O., Meuller, J., Axelsson, M., Bergkvist, A., Johansson, C., Goran Karlsson, B. and Rydstrom, J. Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties. Biochim. Biophys. Acta 1457 (2000) 211-228. [PMID: 10773166]
6. White, S.A., Peake, S.J., McSweeney, S., Leonard, G., Cotton, N.P. and Jackson, J.B. The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria. Structure 8 (2000) 1-12. [PMID: 10673423]
7. Johansson, T., Oswald, C., Pedersen, A., Tornroth, S., Okvist, M., Karlsson, B.G., Rydstrom, J. and Krengel, U. X-ray structure of domain I of the proton-pumping membrane protein transhydrogenase from Escherichia coli. J. Mol. Biol. 352 (2005) 299-312. [PMID: 16083909]
8. Meimaridou, E., Kowalczyk, J., Guasti, L., Hughes, C.R., Wagner, F., Frommolt, P., Nurnberg, P., Mann, N.P., Banerjee, R., Saka, H.N., Chapple, J.P., King, P.J., Clark, A.J. and Metherell, L.A. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat. Genet. 44 (2012) 740-742. [PMID: 22634753]
Accepted name: NADH:ubiquinone reductase (H+-translocating)
Reaction: NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
Other name(s): ubiquinone reductase (ambiguous); type 1 dehydrogenase; complex 1 dehydrogenase; coenzyme Q reductase (ambiguous); complex I (electron transport chain); complex I (mitochondrial electron transport); complex I (NADH:Q1 oxidoreductase); dihydronicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); DPNH-coenzyme Q reductase (ambiguous); DPNH-ubiquinone reductase (ambiguous); mitochondrial electron transport complex 1; mitochondrial electron transport complex I; NADH coenzyme Q1 reductase; NADH-coenzyme Q oxidoreductase (ambiguous); NADH-coenzyme Q reductase (ambiguous); NADH-CoQ oxidoreductase (ambiguous); NADH-CoQ reductase (ambiguous); NADH-ubiquinone reductase (ambiguous); NADH-ubiquinone oxidoreductase (ambiguous); NADH-ubiquinone-1 reductase; reduced nicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); NADH:ubiquinone oxidoreductase complex; NADH-Q6 oxidoreductase (ambiguous); electron transfer complex I; NADH2 dehydrogenase (ubiquinone)
Systematic name: NADH:ubiquinone oxidoreductase
Comments: A flavoprotein (FMN) containing iron-sulfur clusters. The complex is present in mitochondria and aerobic bacteria. Breakdown of the complex can release EC 1.6.99.3, NADH dehydrogenase. In photosynthetic bacteria, reversed electron transport through this enzyme can reduce NAD+ to NADH.
References:
1. Hatefi, Y., Ragan, C.I. and Galante, Y.M. The enzymes and the enzyme complexes of the mitochondrial oxidative phosphorylation system. In: Martonosi, A. (Ed.), The Enzymes of Biological Membranes, 2nd edn, vol. 4, Plenum Press, New York, 1985, pp. 1-70.
2. Herter, S.M., Kortluke, C.M. and Drews, G. Complex I of Rhodobacter capsulatus and its role in reverted electron transport. Arch. Microbiol. 169 (1998) 98-105. [PMID: 9446680]
3. Hunte, C., Zickermann, V. and Brandt, U. Functional modules and structural basis of conformational coupling in mitochondrial complex I. Science 329 (2010) 448-451. [PMID: 20595580]
4. Efremov, R.G., Baradaran, R. and Sazanov, L.A. The architecture of respiratory complex I. Nature 465 (2010) 441-445. [PMID: 20505720]
5. Wikstrom, M. and Hummer, G. Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications. Proc. Natl. Acad. Sci. USA 109 (2012) 4431-4436. [PMID: 22392981]
EC 7.1 Catalysing the translocation of hydrons
EC 7.1.2 Hydron translocation linked to the hydrolysis of a nucleoside triphosphate
Accepted name: H+-exporting ATPase
Reaction: ATP + H2O + H+[side 1] = ADP + phosphate + H+[side 2]
Other name(s): proton-translocating ATPase; yeast plasma membrane H+-ATPase; yeast plasma membrane ATPase; ATP phosphohydrolase (ambiguous)
Systematic name: ATP phosphohydrolase (H+-exporting)
Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme occurs in protozoa, fungi and plants, and generates an electrochemical potential gradient of protons across the plasma membrane.
References:
1. Goffeau, A. and Slayman, C. The proton-translocating ATPase of the fungal plasma membrane. Biochim. Biophys. Acta 639 (1981) 197-223. [PMID: 6461354]
2. Serrano, R., Kielland-Brandt, M.C. and Fink, G.R. Yeast plasma membrane ATPase is essential for growth and has homology with (Na++K+)-, K+-and Ca2+-ATPases. Nature 319 (1986) 689-693. [PMID: 3005867]
3. Serrano, R. and Portillo, F. Catalytic and regulatory sites of yeast plasma membrane H+-ATPase studied by directed mutagenesis. Biochim. Biophys. Acta 1018 (1990) 195-199. [PMID: 2144186]
4. Perlin, D.S., San Francisco, M.J., Slayman, C.W. and Rosen, B.P. H+/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch. Biochem. Biophys. 248 (1986) 53-61. [PMID: 2425739]
Accepted name: H+-transporting two-sector ATPase
Reaction: ATP + H2O + 4 H+[side 1] = ADP + phosphate + 4 H+[side 2]
Glossary: In Fo, the "o" refers to oligomycin. F0 is incorrect
Other name(s): ATP synthase; F1-ATPase; FoF1-ATPase; H+-transporting ATPase; mitochondrial ATPase; coupling factors (F0, F1 and CF1); chloroplast ATPase; bacterial Ca2+/Mg2+ ATPase
Systematic name: ATP phosphohydrolase (H+-transporting)
Comments: A multisubunit non-phosphorylated ATPase that is involved in the transport of ions. Large enzymes of mitochondria, chloroplasts and bacteria with a membrane sector (Fo, Vo, Ao) and a cytoplasmic-compartment sector (F1, V1, A1). The F-type enzymes of the inner mitochondrial and thylakoid membranes act as ATP synthases. All of the enzymes included here operate in a rotational mode, where the extramembrane sector (containing 3 α- and 3 β-subunits) is connected via the δ-subunit to the membrane sector by several smaller subunits. Within this complex, the γ- and ε-subunits, as well as the 9-12 c subunits rotate by consecutive 120° angles and perform parts of ATP synthesis. This movement is driven by the H+ electrochemical potential gradient. The V-type (in vacuoles and clathrin-coated vesicles) and A-type (archaeal) enzymes have a similar structure but, under physiological conditions, they pump H+ rather than synthesize ATP.
References:
1. Perlin, D.S., San Francisco, M.J., Slayman, C.W. and Rosen, B.P. H+/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch. Biochem. Biophys. 248 (1986) 53-61. [PMID: 2425739]
2. Boyer, P.D. The binding change mechanism for ATP synthase - some probabilities and possibilities. Biochim. Biophys. Acta 1140 (1993) 215-250. [PMID: 8417777]
3. Abrahams, J.P., Leslie, A.G.W., Lutter, R. and Walker, J.F. Structure at 2.8 Å resolution of F1-ATPase from bovine heart mitochondria. Nature 375 (1994) 621-628. [PMID: 8065448]
4. Blair, A., Ngo, L., Park, J., Paulsen, I.T. and Saier, M.H., Jr. Phylogenetic analyses of the homologous transmembrane channel-forming proteins of the FoF1-ATPases of bacteria, chloroplasts and mitochondria. Microbiology 142 (1996) 17-32. [PMID: 8581162]
5. Noji, H., Yasuda, R., Yoshida, M. and Kinosita, K., Jr. Direct observation of the rotation of F1-ATPase. Nature 386 (1997) 299-302. [PMID: 9069291]
6. Turina, P., Samoray, D. and Graber, P. H+/ATP ratio of proton transport-coupled ATP synthesis and hydrolysis catalysed by CF0F1-liposomes. EMBO J. 22 (2003) 418-426. [PMID: 12554643]
EC 7.1 Catalysing the translocation of hydrons
EC 7.1.3 Hydron translocation linked to the hydrolysis of diphosphate
Accepted name: H+-exporting diphosphatase
Reaction: diphosphate + H2O + H+[side 1] = 2 phosphate + H+[side 2]
Other name(s): H+-PPase; proton-pumping pyrophosphatase; vacuolar H+-pyrophosphatase; hydrogen-translocating pyrophosphatase; proton-pumping dihosphatase
Systematic name: diphosphate phosphohydrolase (H+-transporting)
Comments: This enzyme, found in plants and fungi, couples the energy from diphosphate hydrolysis to active proton translocation across the tonoplast into the vacuole. The enzyme acts cooperatively with cytosolic soluble diphosphatases to regulate the cytosolic diphosphate level.
References:
1. Rea, P.A. and Poole, R.J. Chromatographic resolution of H+-translocating pyrophosphatase from H+-translocating ATPase of higher plant tonoplast. Plant Physiol. 81 (1986) 126-129. [PMID: 16664761]
2. Sarafian, V. and Poole, R.J. Purification of an H+-translocating inorganic pyrophosphatase from vacuole membranes of red beet. Plant Physiol. 91 (1989) 34-38. [PMID: 16667022]
3. Hedrich, R., Kurkdjian, A., Guern, J. and Flugge, U.I. Comparative studies on the electrical properties of the H+ translocating ATPase and pyrophosphatase of the vacuolar-lysosomal compartment. EMBO J. 8 (1989) 2835-2841. [PMID: 2479537]
4. Segami, S., Tomoyama, T., Sakamoto, S., Gunji, S., Fukuda, M., Kinoshita, S., Mitsuda, N., Ferjani, A. and Maeshima, M. Vacuolar H+-pyrophosphatase and cytosolic soluble pyrophosphatases cooperatively regulate pyrophosphate levels in Arabidopsis thaliana, Plant Cell 30 (2018) 1040-1061. [PMID: 29691313]
EC 7.2 Catalysing the translocation of inorganic cations
EC 7.2.1 Linked to oxidoreductase reactions
Accepted name: NADH:ubiquinone reductase (Na+-transporting)
Reaction: NADH + H+ + ubiquinone + n Na+[side 1] = NAD+ + ubiquinol + n Na+[side 2]
Other name(s): Na+-translocating NADH-quinone reductase; (Na+-NQR)
Systematic name: NADH:ubiquinone oxidoreductase (Na+-translocating)
Comments: An iron-sulfur flavoprotein, containing two covalently bound molecules of FMN, one noncovalently bound FAD, one riboflavin, and one [2Fe-2S] cluster.
References:
1. Beattie, P., Tan, K., Bourne, R.M., Leach, D., Rich, P.R. and Ward, F.B. Cloning and sequencing of four structural genes for the Na+-translocating NADH-ubiquinone oxidoreductase of Vibrio alginolyticus. FEBS Lett. 356 (1994) 333-338. [PMID: 7805867]
2. Nakayama, Y., Hayashi, M. and Unemoto, T. Identification of six subunits constituting Na+-translocating NADH-quinone reductase from the marine Vibrio alginolyticus. FEBS Lett. 422 (1998) 240-242. [PMID: 9490015]
3. Bogachev, A.V., Bertsova, Y.V., Barquera, B. and Verkhovsky, M.I. Sodium-dependent steps in the redox reactions of the Na+-motive NADH:quinone oxidoreductase from Vibrio harveyi. Biochemistry 40 (2001) 7318-7323. [PMID: 11401580]
4. Barquera, B., Hellwig, P., Zhou, W., Morgan, J.E., Hase, C.C., Gosink, K.K., Nilges, M., Bruesehoff, P.J., Roth, A., Lancaster, C.R. and Gennis, R.B. Purification and characterization of the recombinant Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae. Biochemistry 41 (2002) 3781-3789. [PMID: 11888296]
5. Barquera, B., Nilges, M.J., Morgan, J.E., Ramirez-Silva, L., Zhou, W. and Gennis, R.B. Mutagenesis study of the 2Fe-2S center and the FAD binding site of the Na+-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae. Biochemistry 43 (2004) 12322-12330. [PMID: 15379571]
Accepted name: ferredoxin—NAD+ oxidoreductase (Na+-transporting)
Reaction: 2 reduced ferredoxin [iron-sulfur] cluster + NAD+ + H+ + Na+[side 1] = 2 oxidized ferredoxin [iron-sulfur] cluster + NADH + Na+[side 2]
Other name(s): Rnf complex (ambiguous); Na+-translocating ferredoxin:NAD+ oxidoreductase
Systematic name: ferredoxin:NAD+ oxidoreductase (Na+-transporting)
Comments: This iron-sulfur and flavin-containing electron transport complex, isolated from the bacterium Acetobacterium woodii, couples the energy from reduction of NAD+ by ferredoxin to pumping sodium ions out of the cell, generating a gradient across the cytoplasmic membrane.
References:
1. Biegel, E., Schmidt, S. and Muller, V. Genetic, immunological and biochemical evidence for a Rnf complex in the acetogen Acetobacterium woodii. Environ Microbiol 11 (2009) 1438-1443. [PMID: 19222539]
2. Biegel, E. and Muller, V. Bacterial Na+-translocating ferredoxin:NAD+ oxidoreductase. Proc. Natl. Acad. Sci. USA 107 (2010) 18138-18142. [PMID: 20921383]
3. Hess, V., Schuchmann, K. and Muller, V. The ferredoxin:NAD+ oxidoreductase (Rnf) from the acetogen Acetobacterium woodii requires Na+ and is reversibly coupled to the membrane potential. J. Biol. Chem. 288 (2013) 31496-31502. [PMID: 24045950]
EC 7.2 Catalysing the translocation of inorganic cations
EC 7.2.2 Linked to the hydrolysis of a nucleoside triphosphate
Accepted name: Na+-transporting two-sector ATPase
Reaction: ATP + H2O + Na+[side 1] = ADP + phosphate + Na+[side 2]
Systematic name: ATP phosphohydrolase (two-sector, Na+-transporting)
Comments: A multisubunit ATPase transporter found in some halophilic or alkalophilic bacteria that functions in maintaining sodium homeostasis. The enzyme is similar to EC 7.1.2.2 (H+-transporting two-sector ATPase) but pumps Na+ rather than H+. cf. EC 7.2.2.3, P-type Na+ transporter and EC 7.2.2.4, ABC-type Na+ transporter.
References:
1. Solioz, M. and Davies, K. Operon of vacuolar-type Na+-ATPase of Enterococcus hirae. J. Biol. Chem. 269 (1994) 9453-9459. [PMID: 8144530]
2. Takase, K., Kakinuma, S., Yamato, I., Konishi, K., Igarashi, K. and Kanikuma, Y. Sequencing and characterization of the ntp gene cluster for vacuolar-type Na+-translocating ATPase of Enterococcus hirae. J. Biol. Chem. 269 (1994) 11037-11044. [PMID: 8157629]
3. Rahlfs, S. and Müller, V. Sequence of subunit c of the Na+-translocating F1Fo-ATPase of Acetobacterium woodii: proposal for determinants of Na+ specificity as revealed by sequence comparisons. FEBS Lett. 404 (1997) 269-271. [PMID: 9119076]
Accepted name: ABC-type Cd2+ transporter
Reaction: ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
Other name(s): cadmium-transporting ATPase (ambiguous); ABC-type cadmium-transporter
Systematic name: ATP phosphohydrolase (ABC-type, heavy-metal-exporting)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd2+, from the cytosol into the vacuole.
References:
1. Li, Z.S., Szczypka, M., Lu, Y.P., Thiele, D.J. and Rea, P.A. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J. Biol. Chem. 271 (1996) 6509-6517. [PMID: 8626454]
2. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
Accepted name: P-type Na+ transporter
Reaction: ATP + H2O + Na+[side 1] = ADP + phosphate + Na+[side 2]
Other name(s): Na+-exporting ATPase (ambiguous); ENA1 (gene name); ENA2 (gene name); ENA5 (gene name)
Systematic name: ATP phosphohydrolase (P-type, Na+-exporting)
Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme from yeast is involved in the efflux of Na+, with one ion being exported per ATP hydrolysed. Some forms can also export Li+ ions. cf. EC 7.2.2.1, Na+-transporting two-sector ATPase and EC 7.2.2.4, ABC-type Na+ transporter.
References:
1. Wieland, J., Nitsche, A.M., Strayle, J., Steiner, H. and Rudolph, H.K. The PMR2 gene cluster encodes functionally distinct isoforms of a putative Na+ pump in the yeast plasma membrane. EMBO J. 14 (1995) 3870-3882. [PMID: 7664728]
2. Catty, P., de Kerchove d'Exaerde, A. and Goffeau, A. The complete inventory of the yeast Saccharomyces cerevisiae P-type transport ATPases. FEBS Lett. 409 (1997) 325-332. [PMID: 9224683]
3. Benito, B., Quintero, F.J. and Rodriguez-Navarro, A. Overexpression of the sodium ATPase of Saccharomyces cerevisiae: conditions for phosphorylation from ATP and Pi. Biochim. Biophys. Acta 1328 (1997) 214-226. [PMID: 9315618]
4. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
Accepted name: ABC-type Na+ transporter
Reaction: ATP + H2O + Na+[side 1] = ADP + phosphate + Na+[side 2]
Other name(s): natAB (gene names)
Systematic name: ATP phosphohydrolase (ABC-type, Na+-exporting)
Comments: ABC-type (ATP-binding cassette-type) transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. This bacterial enzyme, characterized from Bacillus subtilis, exports Na+ ions out of the cell. cf. EC 7.2.2.1, Na+-transporting two-sector ATPase and EC 7.2.2.3, P-type Na+ transporter.
References:
1. Cheng, J., Guffanti, A.A. and Krulwich, T.A. A two-gene ABC-type transport system that extrudes Na+ in Bacillus subtilis is induced by ethanol or protonophore. Mol. Microbiol. 23 (1997) 1107-1120. [PMID: 9106203]
2. Ogura, M., Tsukahara, K., Hayashi, K. and Tanaka, T. The Bacillus subtilis NatK-NatR two-component system regulates expression of the natAB operon encoding an ABC transporter for sodium ion extrusion. Microbiology 153 (2007) 667-675. [PMID: 17322186]
EC 7.2 Catalysing the translocation of inorganic cations
EC 7.2.4 Linked to decarboxylation
Accepted name: carboxybiotin decarboxylase
Reaction: a carboxybiotinyl-[protein] + n Na+[side 1] + H+[side 2] = CO2 + a biotinyl-[protein] + n Na+[side 2] (n = 1-2)
For diagram of the reaction click here
Other name(s): MadB; carboxybiotin protein decarboxylase
Systematic name: carboxybiotinyl-[protein] carboxy-lyase
Comments: The integral membrane protein MadB from the anaerobic bacterium Malonomonas rubra is a component of the multienzyme complex EC 4.1.1.89, biotin-dependent malonate decarboxylase. The free energy of the decarboxylation reaction is used to pump Na+ out of the cell. The enzyme is a member of the Na+-translocating decarboxylase family, other members of which include EC 7.2.4.2 [oxaloacetate decarboxylase (Na+ extruding)] and EC 7.2.4.3 [(S)-methylmalonyl-CoA decarboxylase (sodium-transporting)] [2].
References:
1. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]
2. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]
Accepted name: oxaloacetate decarboxylase (Na+ extruding)
Reaction: oxaloacetate + 2 Na+[side 1] = pyruvate + CO2 + 2 Na+[side 2]
Other name(s): oxaloacetate β-decarboxylase (ambiguous); oxalacetic acid decarboxylase (ambiguous); oxalate β-decarboxylase (ambiguous); oxaloacetate carboxy-lyase (ambiguous)
Systematic name: oxaloacetate carboxy-lyase (pyruvate-forming; Na+-extruding)
Comments: The enzyme from the bacterium Klebsiella aerogenes is a biotinyl protein and also decarboxylates glutaconyl-CoA and methylmalonyl-CoA. The process is accompanied by the extrusion of two sodium ions from cells. Some animal enzymes require Mn2+. Differs from EC 4.1.1.112 (oxaloacetate decarboxylase) for which there is no evidence for involvement in Na+ transport.
References:
1. Dimroth, P. Characterization of a membrane-bound biotin-containing enzyme: oxaloacetate decarboxylase from Klebsiella aerogenes. Eur. J. Biochem. 115 (1981) 353-358. [PMID: 7016536]
2. Dimroth, P. The role of biotin and sodium in the decarboxylation of oxaloacetate by the membrane-bound oxaloacetate decarboxylase from Klebsiella aerogenes. Eur. J. Biochem. 121 (1982) 435-441. [PMID: 7037395]
Accepted name: (S)-methylmalonyl-CoA decarboxylase (sodium-transporting)
Reaction: (S)-methylmalonyl-CoA + Na+[side 1] + H=[side 2] = propanoyl-CoA + CO2 + Na+[side 2]
Other name(s): methylmalonyl-coenzyme A decarboxylase (ambiguous); (S)-2-methyl-3-oxopropanoyl-CoA carboxy-lyase (incorrect); (S)-methylmalonyl-CoA carboxy-lyase (ambiguous)
Systematic name: (S)-methylmalonyl-CoA carboxy-lyase (propanoyl-CoA-forming, sodium-transporting)
Comments: This bacterial enzyme couples the decarboxylation of (S)-methylmalonyl-CoA to propanoyl-CoA to the vectorial transport of Na+ across the cytoplasmic membrane, thereby creating a sodium ion motive force that is used for ATP synthesis. It is a membrane-associated biotin protein and is strictly dependent on sodium ions for activity.
References:
1. Galivan, J.H. and Allen, S.H.G. Methylmalonyl coenzyme A decarboxylase. Its role in succinate decarboxylation by Micrococcus lactilyticus. J. Biol. Chem. 243 (1968) 1253-1261. [PMID: 5646172]
2. Hilpert, W. and Dimroth, P. Conversion of the chemical energy of methylmalonyl-CoA decarboxylation into a Na+ gradient. Nature 296 (1982) 584-585. [PMID: 7070502]
3. Hoffmann, A., Hilpert, W. and Dimroth, P. The carboxyltransferase activity of the sodium-ion-translocating methylmalonyl-CoA decarboxylase of Veillonella alcalescens. Eur. J. Biochem. 179 (1989) 645-650. [PMID: 2920730]
4. Huder, J.B. and Dimroth, P. Expression of the sodium ion pump methylmalonyl-coenzyme A-decarboxylase from Veillonella parvula and of mutated enzyme specimens in Escherichia coli. J. Bacteriol. 177 (1995) 3623-3630. [PMID: 7601825]
5. Bott, M., Pfister, K., Burda, P., Kalbermatter, O., Woehlke, G. and Dimroth, P. Methylmalonyl-CoA decarboxylase from Propionigenium modestum--cloning and sequencing of the structural genes and purification of the enzyme complex. Eur. J. Biochem. 250 (1997) 590-599. [PMID: 9428714]
EC 7.3 Catalysing the translocation of inorganic anions and their chelates
EC 7.3.2 Linked to the hydrolysis of a nucleoside triphosphate
Accepted name: ABC-type phosphate transporter
Reaction: ATP + H2O + phosphate-[phosphate-binding protein][side 1] = ADP + phosphate + phosphate[side 2] + [phosphate-binding protein][side 1]
Other name(s): phosphate ABC transporter; phosphate-transporting ATPase (ambiguous)
Systematic name: ATP phosphohydrolase (ABC-type, phosphate-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme that interacts with an extracytoplasmic substrate binding protein and mediates the high affinity uptake of phosphate anions. Unlike P-type ATPases, it does not undergo phosphorylation during the transport process.
References:
1. Webb, D.C., Rosenberg, H. and Cox, G.B. Mutational analysis of the Escherichia coli phosphate-specific transport system, a member of the traffic ATPase (or ABC) family of membrane transporters. A role for proline residues in transmembrane helices. J. Biol. Chem. 267 (1992) 24661-24668. [PMID: 1447208]
2. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
3. Braibant, M., LeFevre, P., de Wit, L., Ooms, J., Peirs, P., Huygen, K., Wattiez, R. and Content, J. Identification of a second Mycobacterium tuberculosis gene cluster encoding proteins of an ABC phosphate transporter. FEBS Lett. 394 (1996) 206-212. [PMID: 8843165]
4. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
5. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
Accepted name: ABC-type phosphonate transporter
Reaction: ATP + H2O + phosphonate-[phosphonate-binding protein][side 1] = ADP + phosphate + phosphonate[side 2] + [phosphonate-binding protein][side 1]
Other name(s): phosphonate-transporting ATPase (ambiguous)
Systematic name: ATP phosphohydrolase (ABC-type, phosphonate-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein and mediates the import of phosphonate and organophosphate anions.
References:
1. Wanner, B.L. and Metcalf, W.W. Molecular genetic studies of a 10.9-kb operon in Escherichia coli for phosphonate uptake and biodegradation. FEMS Microbiol. Lett. 79 (1992) 133-139. [PMID: 1335942]
2. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
3. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
4. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
EC 7.4 Catalysing the translocation amino acids and peptides
EC 7.4.2 Linked to the hydrolysis of a nucleoside triphosphate
Accepted name: ABC-type polar-amino-acid transporter
Reaction: ATP + H2O + polar amino acid-[polar amino acid-binding protein][side 1] = ADP + phosphate + polar amino acid[side 2] + [polar amino acid-binding protein][side 1]
Glossary: nopaline = N-{(1R)-1-carboxy-4-[(diaminomethylene)amino]butyl}-L-glutamate
Other name(s): histidine permease; polar-amino-acid-transporting ATPase
Systematic name: ATP phosphohydrolase (ABC-type, polar-amino-acid-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein and mediates the import of polar amino acids. This entry comprises bacterial enzymes that import His, Arg, Lys, Glu, Gln, Asp, ornithine, octopine and nopaline.
References:
1. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
2. Nikaido, K., Liu, P.Q. and Ferro-Luzzi Ames, G. Purification and characterization of HisP, the ATP-binding subunit of a traffic ATPase (ABC transporter), the histidine permease of Salmonella typhimurium. Solubilization, dimerization , and ATPase activity. J. Biol. Chem. 272 (1997) 27745-27752. [PMID: 9346917]
3. Walshaw, D.L., Lowthorpe, S., East, A. and Poole, P.S. Distribution of a sub-class of bacterial ABC polar amino acid transporter and identification of an N-terminal region involved in solute specificity. FEBS Lett. 414 (1997) 397-401. [PMID: 9315727]
4. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
Accepted name: ABC-type nonpolar-amino-acid transporter
Reaction: ATP + H2O + nonpolar amino acid-[nonpolar amino acid-binding protein][side 1] = ADP + phosphate + nonpolar amino acid[side 2] + [nonpolar amino acid-binding protein][side 1]
Other name(s): nonpolar-amino-acid-transporting ATPase
Systematic name: ATP phosphohydrolase (ABC-type, nonpolar-amino-acid-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein. This entry comprises enzymes that import Leu, Ile and Val.
References:
1. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
2. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
3. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
EC 7.5 Catalysing the translocation carbohydrates and their derivatives
EC 7.5.2 Linked to the hydrolysis of a nucleoside triphosphate
Accepted name: ABC-type maltose transporter
Reaction: ATP + H2O + maltose-[maltose-binding protein][side 1] = ADP + phosphate + maltose[side 2] + [maltose-binding protein][side 1]
Other name(s): maltose ABC transporter; maltose-transporting ATPase
Systematic name: ATP phosphohydrolase (ABC-type, maltose-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein and mediates the import of maltose and maltose oligosaccharides.
References:
1. Higgins, C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8 (1992) 67-113. [PMID: 1282354]
2. Dassa, E. and Muir, S. Membrane topology of MalG, an inner membrane protein from the maltose transport system of Escherichia coli. Mol. Microbiol. 7 (1993) 29-38. [PMID: 8437518]
3. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
4. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
5. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
Accepted name: ABC-type oligosaccharide transporter
Reaction: ATP + H2O + oligosaccharide-[oligosaccharide-binding protein][side 1] = ADP + phosphate + oligosaccharide[side 2] + [oligosaccharide-binding protein][side 1]
Other name(s): oligosaccharide-transporting ATPase
Systematic name: ATP phosphohydrolase (ABC-type, oligosaccharide-importing)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein and mediates the import of lactose, melibiose and raffinose.
References:
1. Higgins, C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8 (1992) 67-113. [PMID: 1282354]
2. Williams, S.G., Greenwood, J.A. and Jones, C.W. Molecular analysis of the lac operon encoding the binding-protein-dependent lactose transport system and β-galactosidase in Agrobacterium radiobacter. Mol. Microbiol. 6 (1992) 1755-1768. [PMID: 1630315]
3. Tam, R. and Saier, M.H., Jr. Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol. Rev. 57 (1993) 320-346. [PMID: 8336670]
4. Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271-278. [PMID: 7569321]
5. Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81-136. [PMID: 9889977]
EC 7.6 Catalysing the translocation of other compounds
EC 7.6.2 Linked to the hydrolysis of a nucleoside triphosphate
Accepted name: P-type phospholipid transporter
Reaction: ATP + H2O + phospholipid[side 1] = ADP + phosphate + phospholipid[side 2]
Other name(s): Mg2+-ATPase (ambiguous); flippase (ambiguous); aminophospholipid-transporting ATPase (ambiguous); phospholipid-translocating ATPase (ambiguous)
Systematic name: ATP phosphohydrolase (P-type, phospholipid-flipping)
Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme moves phospholipids such as phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine from one membrane face to the other (‘flippase’).
References:
1. Morris, M.B., Auland, M.E., Xu, Y.H. and Roufogalis, B.D. Characterization of the Mg2+-ATPase activity of the human erythrocyte membrane. Biochem. Mol. Biol. Int. 31 (1993) 823-832. [PMID: 8136700]
2. Vermeulen, W.P., Briede, J.J. and Rolofsen, B. Manipulation of the phosphatidylethanolamine pool in the human red cell membrane affects its Mg2+-ATPase activity. Mol. Membr. Biol. 13 (1996) 95-102. [PMID: 8839453]
3. Suzuki, H., Kamakura, M., Morii, M. and Takeguchi, N. The phospholipid flippase activity of gastric vesicles. J. Biol. Chem. 272 (1997) 10429-10434. [PMID: 9099684]
4. Auland, M.E., Roufogalis, B.D., Devaux, P.F. and Zachowski, A. Reconstitution of ATP-dependent aminophospholipid translocation in proteoliposomes. Proc. Natl. Acad. Sci. USA 91 (1994) 10938-10942. [PMID: 7971987]
5. Alder-Baerens, N., Lisman, Q., Luong, L., Pomorski, T. and Holthuis, J.C. Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol. Biol. Cell 17 (2006) 1632-1642. [PMID: 16452632]
6. Lopez-Marques, R.L., Poulsen, L.R., Hanisch, S., Meffert, K., Buch-Pedersen, M.J., Jakobsen, M.K., Pomorski, T.G. and Palmgren, M.G. Intracellular targeting signals and lipid specificity determinants of the ALA/ALIS P4-ATPase complex reside in the catalytic ALA α-subunit. Mol. Biol. Cell 21 (2010) 791-801. [PMID: 20053675]
Accepted name: ABC-type xenobiotic transporter
Reaction: ATP + H2O + xenobiotic[side 1] = ADP + phosphate + xenobiotic[side 2]
Other name(s): xenobiotic-transporting ATPase; multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting)
Systematic name: ATP phosphohydrolase (ABC-type, xenobiotic-exporting)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. The enzymes from Gram-positive bacteria and eukaryotic cells export a number of drugs with unusual specificity, covering various groups of unrelated substances while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them also transport glutathione—drug conjugates (see EC 7.6.2.3, ABC-type glutathione-S-conjugate transporter) while others also show some ‘flippase’ activity (redundant, but not identical, to EC 7.6.2.1, P-type phospholipid transporter).
References:
1. Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36 (1996) 161-183. [PMID: 8725386]
2. Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude-Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression. Adv. Enzyme Regul. 36 (1996) 351-363. [PMID: 8869755]
3. Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv. Enzyme Regul. 37 (1997) 321-333. [PMID: 9381978]
4. Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the Mr 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58 (1998) 5130-5136. [PMID: 9823323]
5. van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31-36. [PMID: 9693718]
6. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
7. Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995) 320-329. [PMID: 7614555]
8. Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M. bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. J. Bacteriol. 177 (1995) 1536-1543. [PMID: 7883711]
9. Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167-25172. [PMID: 8810273]
Accepted name: ABC-type glutathione-S-conjugate transporter
Reaction: ATP + H2O + glutathione-S-conjugate[side 1] = ADP + phosphate + glutathione-S-conjugate[side 2]
Other name(s): multidrug resistance-associated protein 1; glutathione-S-conjugate-translocating ATPase; MRP; MRP1; ABCC1 (gene name); YBT1 (gene name); YCF1 (gene name)
Systematic name: ATP phosphohydrolase (ABC-type, glutathione-S-conjugate-exporting)
Comments: A eukaryotic ATP-binding cassette (ABC) type transporter that mediates the transport of glutathione-S-conjugates. The mammalian enzyme, which also transports some glucuronides, exports the substrates out of the cell, while plant and fungal transporters export them into the vacuole. Over-expression confers resistance to anticancer drugs by their efficient exportation in glutathione-S-conjugate form.
References:
1. Zaman, G.J., Flens, M.J., van Leusden, M.R., de Haas, M., Mulder, H.S., Lankelma, J., Pinedo, H.M., Scheper, R.J., Baas, F., Broxterman, H.J. and et al. The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. Proc. Natl Acad. Sci. USA 91 (1994) 8822-8826. [PMID: 7916458]
2. Lautier, D., Canitrot, Y., Deeley, R.G. and Cole, S.P. Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem. Pharmacol. 52 (1996) 967-977. [PMID: 8831715]
3. Li, Z.S., Szczypka, M., Lu, Y.P., Thiele, D.J. and Rea, P.A. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J. Biol. Chem. 271 (1996) 6509-6517. [PMID: 8626454]
4. Lu, Y.P., Li, Z.S. and Rea, P.A. AtMRP1 gene of Arabidopsis encodes a glutathione S-conjugate pump: isolation and functional definition of a plant ATP-binding cassette transporter gene. Proc. Natl Acad. Sci. USA 94 (1997) 8243-8248. [PMID: 9223346]
5. Cole, S.P. Multidrug resistance protein 1 (MRP1, ABCC1), a "multitasking" ATP-binding cassette (ABC) transporter. J. Biol. Chem 289 (2014) 30880-30888. [PMID: 25281745]
6. Cordente, A.G., Capone, D.L. and Curtin, C.D. Unravelling glutathione conjugate catabolism in Saccharomyces cerevisiae: the role of glutathione/dipeptide transporters and vacuolar function in the release of volatile sulfur compounds 3-mercaptohexan-1-ol and 4-mercapto-4-methylpentan-2-one. Appl. Microbiol. Biotechnol. 99 (2015) 9709-9722. [PMID: 26227410]