An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Common name: phosphoglycerate dehydrogenase
Reaction: (1) 3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH + H+
(2) 2-hydroxyglutarate + NAD+ = 2-oxoglutarate + NADH + H+
For diagram click here.
Other name(s): D-3-phosphoglycerate:NAD+ oxidoreductase; α-phosphoglycerate dehydrogenase; 3-phosphoglycerate dehydrogenase; 3-phosphoglyceric acid dehydrogenase; D-3-phosphoglycerate dehydrogenase; glycerate 3-phosphate dehydrogenase; glycerate-1,3-phosphate dehydrogenase; phosphoglycerate oxidoreductase; phosphoglyceric acid dehydrogenase; SerA; 3-phosphoglycerate:NAD+ 2-oxidoreductase; SerA 3PG dehydrogenase; 3PHP reductase; αKG reductase; D- and L-HGA
Systematic name: 3-phospho-D-glycerate:NAD+ 2-oxidoreductase
Comments: This enzyme catalyses the first committed step in the phosphoserine pathway of serine biosynthesis in Escherichia coli [2,3]. Reaction (1) occurs predominantly in the reverse direction and is inhibited by serine and glycine. The enzyme is unusual in that it also acts as a D- and L-2-hydroxyglutarate dehydrogenase (with the D-form being the better substrate) and as a 2-oxoglutarate reductase [3]. It has been postulated [3] that the cellular 2-oxoglutarate concentration may regulate serine biosynthesis and one-carbon metabolism directly by modulating the activity of this enzyme.
Links to other databases: BRENDA, ERGO, EXPASY, GTD, KEGG, PDB, CAS registry number: 9075-29-0
References:
1. Sugimoto, E. and Pizer, L.I. The mechanism of end product inhibition of serine biosynthesis. I. Purification and kinetics of phosphoglycerate dehydrogenase. J. Biol. Chem. 243 (1968) 2081-1089. [PMID: 4384871]
2. Pizer, L.I. The pathway and control of serine biosynthesis in Escherichia coli. J. Biol. Chem. 238 (1963) 3934-3944. [PMID: 14086727]
3. Zhao, G. and Winkler, M.E. A novel α-ketoglutarate reductase activity of the serA-encoded 3-phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria. J. Bacteriol. 178 (1996) 232-239. [PMID: 8550422]
4. Schuller, D.J., Grant, G.A. and Banaszak, L.J. The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate dehydrogenase. Nat. Struct. Biol. 2 (1995) 69-76. [PMID: 7719856]
Common name: pyruvate oxidase
Reaction: pyruvate + phosphate + O2 = acetyl phosphate + CO2 + H2O2
Glossary: thiamine diphosphate = 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-diphosphoethyl)-4-methyl-1,3-thiazolium
Other name(s): pyruvic oxidase; phosphate-dependent pyruvate oxidase
Systematic name: pyruvate:oxygen 2-oxidoreductase (phosphorylating)
Comments: A flavoprotein (FAD) requiring thiamine diphosphate. Two reducing equivalents are transferred from the resonant carbanion/enamine forms of 2-hydroxyethyl-thiamine-diphosphate to the adjacent flavin cofactor, yielding 2-acetyl-thiamine diphosphate (AcThDP) and reduced flavin. FADH2 is reoxidized by O2 to yield H2O2 and FAD and AcThDP is cleaved phosphorolytically to acetyl phosphate and thiamine diphosphate [2].
Links to other databases: BRENDA, ERGO, EXPASY, GO, KEGG, PDB, CAS registry number: 9001-96-1
References:
1. Williams, F.R. and Hager, L.P. Crystalline flavin pyruvate oxidase from Escherichia coli. I. Isolation and properties of the flavoprotein. Arch. Biochem. Biophys. 116 (1966) 168-176. [PMID: 5336022]
2. Tittmann, K., Wille, G., Golbik, R., Weidner, A., Ghisla, S. and Hübner, G. Radical phosphate transfer mechanism for the thiamin diphosphate- and FAD-dependent pyruvate oxidase from Lactobacillus plantarum. Kinetic coupling of intercofactor electron transfer with phosphate transfer to acetyl-thiamin diphosphate via a transient FAD semiquinone/hydroxyethyl-ThDP radical pair. Biochemistry 44 (2005) 13291-13303. [PMID: 16201755]
Common name: lysine 6-dehydrogenase
Reaction: (1a) L-lysine + NAD+ + H2O = (S)-2-aminoadipate 6-semialdehyde + NADH + H+ + NH3
(1b) (S)-2-aminoadipate 6-semialdehyde = (S)-2,3,4,5-tetrahydropiperidine-2-carboxylate + H2O (spontaneous)
For diagram click here.
Glossary: (S)-2-aminoadipate 6-semialdehyde = L-allysine = (S)-2-amino-6-oxohexanoate
(S)-2,3,4,5-tetrahydropyridine-2-carboxylate = (S)-1,6-didehydropiperidine-2-carboxylate
Other name(s): L-lysine ε-dehydrogenase; L-lysine 6-dehydrogenase; LysDH
Systematic name: L-lysine:NAD+ 6-oxidoreductase (deaminating)
Comments: The enzyme is highly specific for L-lysine as substrate, although (S)-(β-aminoethyl)-L-cysteine can act as a substrate, but more slowly. While the enzyme from Agrobacterium tumefaciens can use only NAD+, that from the thermophilic bacterium Geobacillus stearothermophilus can also use NADP+, but more slowly [1,4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 89400-30-6
References:
1. Misono, H. and Nagasaki, S. Occurrence of L-lysine ε-dehydrogenase in Agrobacterium tumefaciens. J. Bacteriol. 150 (1982) 398-401. [PMID: 6801024]
2. Misono, H., Uehigashi, H., Morimoto, E. and Nagasaki, S. Purification and properties of L-lysine ε-dehydrogenase from Agrobacterium tumefaciens. Agric. Biol. Chem. 49 (1985) 2253-2255.
3. Misono, H., Hashimoto, H., Uehigashi, H., Nagata, S. and Nagasaki, S. Properties of L-lysine ε-dehydrogenase from Agrobacterium tumefaciens. J. Biochem. (Tokyo) 105 (1989) 1002-1008. [PMID: 2768207]
4. Heydari, M., Ohshima, T., Nunoura-Kominato, N. and Sakuraba, H. Highly stable L-lysine 6-dehydrogenase from the thermophile Geobacillus stearothermophilus isolated from a Japanese hot spring: characterization, gene cloning and sequencing, and expression. Appl. Environ. Microbiol. 70 (2004) 937-942. [PMID: 14766574]
Common name: 1-pyrroline dehydrogenase
Reaction: 1-pyrroline + NAD+ + 2 H2O = 4-aminobutanoate + NADH + 2 H+
For diagram click here.
Glossary: 1-pyrroline = 3,4-dihydro-2H-pyrrole
Other name(s): γ-aminobutyraldehyde dehydrogenase; ABALDH; YdcW
Systematic name: 1-pyrroline:NAD+ oxidoreductase
Comments: 1-Pyrroline forms spontaneously from 4-aminobutanal, produced by EC 2.6.1.82, putrescine aminotransferase. This enzyme forms part of the arginine-catabolism pathway [3].
References:
1. Prieto-Santos, M.I., Martin-Checa, J., Balaña-Fouce, R. and Garrido-Pertierra, A. A pathway for putrescine catabolism in Escherichia coli. Biochim. Biophys. Acta 880 (1986) 242-244. [PMID: 3510672]
2. Prieto, M.I., Martin, J., Balaña-Fouce, R. and Garrido-Pertierra, A. Properties of γ-aminobutyraldehyde dehydrogenase from Escherichia coli. Biochimie 69 (1987) 1161-1168. [PMID: 3129020]
3. Samsonova, N.N., Smirnov, S.V., Novikova, A.E. and Ptitsyn, L.R. Identification of Escherichia coli K12 YdcW protein as a γ-aminobutyraldehyde dehydrogenase. FEBS Lett. 579 (2005) 4107-4112. [PMID: 16023116]
[EC 1.8.4.5 Transferred entry: methionine-S-oxide reductase. Now EC 1.8.4.13, L-methionine (S)-S-oxide reductase and EC 1.8.4.14, L-methionine (R)-S-oxide reductase. (EC 1.8.4.5 created 1984, deleted 2006)]
[EC 1.8.4.6 Transferred entry: protein-methionine-S-oxide reductase. Proved to be due to EC 1.8.4.11, peptide-methionine (S)-S-oxide reductase. (EC 1.8.4.6 created 1984, deleted 2006)]
Common name: peptide-methionine (S)-S-oxide reductase
Reaction: (1) peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (S)-S-oxide + thioredoxin
(2) L-methionine + thioredoxin disulfide + H2O = L-methionine (S)-S-oxide + thioredoxin
For diagram click here and mechanism click here.
Other name(s): MsrA; methionine sulfoxide reductase (ambiguous); methionine sulphoxide reductase A; methionine S-oxide reductase (ambiguous); methionine S-oxide reductase (S-form oxidizing); methionine sulfoxide reductase A; peptide methionine sulfoxide reductase
Systematic name: peptide-L-methionine:thioredoxin-disulfide S-oxidoreductase [L-methionine (S)-S-oxide-forming]
Comments: The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for the reduction of the S-form of L-methionine S-oxide, acting faster on the residue in a peptide than on the free amino acid [9]. On the free amino acid, it can also reduce D-methionine (S)-S-oxide but more slowly [9]. The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.12, methionine (R)-S-oxide reductase, are found within the same protein whereas, in other species, they are separate proteins [1,4]. The reaction proceeds via a sulfenic-acid intermediate [5,10].
References:
1. Moskovitz, J., Singh, V.K., Requena, J., Wilkinson, B.J., Jayaswal, R.K. and Stadtman, E.R. Purification and characterization of methionine sulfoxide reductases from mouse and Staphylococcus aureus and their substrate stereospecificity. Biochem. Biophys. Res. Commun. 290 (2002) 62-65. [PMID: 11779133]
2. Taylor, A.B., Benglis, D.M., Jr., Dhandayuthapani, S. and Hart, P.J. Structure of Mycobacterium tuberculosis methionine sulfoxide reductase A in complex with protein-bound methionine. J. Bacteriol. 185 (2003) 4119-4126. [PMID: 12837786]
3. Singh, V.K. and Moskovitz, J. Multiple methionine sulfoxide reductase genes in Staphylococcus aureus: expression of activity and roles in tolerance of oxidative stress. Microbiology 149 (2003) 2739-2747. [PMID: 14523107]
4. Boschi-Muller, S., Olry, A., Antoine, M. and Branlant, G. The enzymology and biochemistry of methionine sulfoxide reductases. Biochim. Biophys. Acta 1703 (2005) 231-238. [PMID: 15680231]
5. Ezraty, B., Aussel, L. and Barras, F. Methionine sulfoxide reductases in prokaryotes. Biochim. Biophys. Acta 1703 (2005) 221-229. [PMID: 15680230]
6. Weissbach, H., Resnick, L. and Brot, N. Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage. Biochim. Biophys. Acta 1703 (2005) 203-212. [PMID: 15680228]
7. Kauffmann, B., Aubry, A. and Favier, F. The three-dimensional structures of peptide methionine sulfoxide reductases: current knowledge and open questions. Biochim. Biophys. Acta 1703 (2005) 249-260. [PMID: 15680233]
8. Vougier, S., Mary, J. and Friguet, B. Subcellular localization of methionine sulphoxide reductase A (MsrA): evidence for mitochondrial and cytosolic isoforms in rat liver cells. Biochem. J. 373 (2003) 531-537. [PMID: 12693988]
9. Olry, A., Boschi-Muller, S., Marraud, M., Sanglier-Cianferani, S., Van Dorsselear, A. and Branlant, G. Characterization of the methionine sulfoxide reductase activities of PILB, a probable virulence factor from Neisseria meningitidis. J. Biol. Chem. 277 (2002) 12016-12022. [PMID: 11812798]
10. Boschi-Muller, S., Olry, A., Antoine, M. and Branlant, G. The enzymology and biochemistry of methionine sulfoxide reductases. Biochim. Biophys. Acta 1703 (2005) 231-238. [PMID: 15680231]
11. Brot, N., Weissbach, L., Werth, J. and Weissbach, H. Enzymatic reduction of protein-bound methionine sulfoxide. Proc. Natl. Acad. Sci. USA 78 (1981) 2155-2158. [PMID: 7017726]
Common name: peptide-methionine (R)-S-oxide reductase
Reaction: peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
For diagram click here and mechanism click here.
Other name(s): MsrB; methionine sulfoxide reductase (ambiguous); pMSR; methionine S-oxide reductase (ambiguous); selenoprotein R; methionine S-oxide reductase (R-form oxidizing); methionine sulfoxide reductase B; SelR; SelX; PilB; pRMsr
Systematic name: peptide-methionine:thioredoxin-disulfide S-oxidoreductase [methionine (R)-S-oxide-forming]
Comments: The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide [9]. While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater [10]. The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.11, peptide-methionine (S)-S-oxide reductase, are found within the same protein whereas in other species, they are separate proteins [3,5]. The reaction proceeds via a sulfenic-acid intermediate [5,10]. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well [11]. The enzyme from some species contains selenocysteine and Zn2+.
References:
1. Moskovitz, J., Singh, V.K., Requena, J., Wilkinson, B.J., Jayaswal, R.K. and Stadtman, E.R. Purification and characterization of methionine sulfoxide reductases from mouse and Staphylococcus aureus and their substrate stereospecificity. Biochem. Biophys. Res. Commun. 290 (2002) 62-65. [PMID: 11779133]
2. Taylor, A.B., Benglis, D.M., Jr., Dhandayuthapani, S. and Hart, P.J. Structure of Mycobacterium tuberculosis methionine sulfoxide reductase A in complex with protein-bound methionine. J. Bacteriol. 185 (2003) 4119-4126. [PMID: 12837786]
3. Singh, V.K. and Moskovitz, J. Multiple methionine sulfoxide reductase genes in Staphylococcus aureus: expression of activity and roles in tolerance of oxidative stress. Microbiology 149 (2003) 2739-2747. [PMID: 14523107]
4. Boschi-Muller, S., Olry, A., Antoine, M. and Branlant, G. The enzymology and biochemistry of methionine sulfoxide reductases. Biochim. Biophys. Acta 1703 (2005) 231-238. [PMID: 15680231]
5. Ezraty, B., Aussel, L. and Barras, F. Methionine sulfoxide reductases in prokaryotes. Biochim. Biophys. Acta 1703 (2005) 221-229. [PMID: 15680230]
6. Weissbach, H., Resnick, L. and Brot, N. Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage. Biochim. Biophys. Acta 1703 (2005) 203-212. [PMID: 15680228]
7. Kauffmann, B., Aubry, A. and Favier, F. The three-dimensional structures of peptide methionine sulfoxide reductases: current knowledge and open questions. Biochim. Biophys. Acta 1703 (2005) 249-260. [PMID: 15680233]
8. Vougier, S., Mary, J. and Friguet, B. Subcellular localization of methionine sulphoxide reductase A (MsrA): evidence for mitochondrial and cytosolic isoforms in rat liver cells. Biochem. J. 373 (2003) 531-537. [PMID: 12693988]
9. Olry, A., Boschi-Muller, S., Marraud, M., Sanglier-Cianferani, S., Van Dorsselear, A. and Branlant, G. Characterization of the methionine sulfoxide reductase activities of PILB, a probable virulence factor from Neisseria meningitidis. J. Biol. Chem. 277 (2002) 12016-12022. [PMID: 11812798]
10. Boschi-Muller, S., Olry, A., Antoine, M. and Branlant, G. The enzymology and biochemistry of methionine sulfoxide reductases. Biochim. Biophys. Acta 1703 (2005) 231-238. [PMID: 15680231]
11. Sagher, D., Brunell, D., Hejtmancik, J.F., Kantorow, M., Brot, N. and Weissbach, H. Thionein can serve as a reducing agent for the methionine sulfoxide reductases. Proc. Natl. Acad. Sci. USA 103 (2006) 8656-8661. [PMID: 16735467]
Common name: L-methionine (S)-S-oxide reductase
Reaction: L-methionine + thioredoxin disulfide + H2O = L-methionine (S)-S-oxide + thioredoxin
For diagram click here and mechanism click here.
Other name(s): fSMsr; methyl sulfoxide reductase I and II; acetylmethionine sulfoxide reductase; methionine sulfoxide reductase; L-methionine:oxidized-thioredoxin S-oxidoreductase; methionine-S-oxide reductase; free-methionine (S)-S-oxide reductase
Systematic name: L-methionine:thioredoxin-disulfide S-oxidoreductase
Comments: Requires NADPH [2]. The reaction occurs in the opposite direction to that given above. Dithiothreitol can replace reduced thioredoxin. L-Methionine (R)-S-oxide is not a substrate [see EC 1.8.4.14, L-methionine (R)-S-oxide reductase].
References:
1. Black, S., Harte, E.M., Hudson, B. and Wartofsky, L. A specific enzymatic reduction of L-(–)methionine sulfoxide and a related nonspecific reduction of diulfides. J. Biol. Chem. 235 (1960) 2910-2916.
2. Ejiri, S.-I., Weissbach, H. and Brot, N. Reduction of methionine sulfoxide to methionine by Escherichia coli. J. Bacteriol. 139 (1979) 161-164. [PMID: 37234]
3. Ejiri, S.-I., Weissbach, H. and Brot, N. The purification of methionine sulfoxide reductase from Escherichia coli. Anal. Biochem. 102 (1980) 393-398. [PMID: 6999943]
4. Weissbach, H., Resnick, L. and Brot, N. Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage. Biochim. Biophys. Acta 1703 (2005) 203-212. [PMID: 15680228]
Common name: L-methionine (R)-S-oxide reductase
Reaction: L-methionine + thioredoxin disulfide + H2O = L-methionine (R)-S-oxide + thioredoxin
For diagram click here and mechanism click here.
Other name(s): fRMsr; FRMsr; free met-R-(o) reductase; free-methionine (R)-S-oxide reductase
Systematic name: L-methionine:thioredoxin-disulfide S-oxidoreductase [L-methionine (R)-S-oxide-forming]
Comments: Requires NADPH. Unlike EC 1.8.4.12, peptide-methionine (R)-S-oxide reductase, this enzyme cannot use peptide-bound methionine (R)-S-oxide as a substrate [1]. Differs from EC 1.8.4.13, L-methionine (S)-S-oxide in that L-methionine (S)-S-oxide is not a substrate.
References:
1. Etienne, F., Spector, D., Brot, N. and Weissbach, H. A methionine sulfoxide reductase in Escherichia coli that reduces the R enantiomer of methionine sulfoxide. Biochem. Biophys. Res. Commun. 300 (2003) 378-382. [PMID: 12504094]
Common name: o-aminophenol oxidase
Reaction: (1a) 2 2-aminophenol + O2 = 2 6-iminocyclohexa-2,4-dienone + 2 H2O
(1b) 2 6-iminocyclohexa-2,4-dienone + oxidant = 2-aminophenoxazin-3-one + reduced oxidant (spontaneous)
For diagram click here.
Glossary: 6-iminocyclohexa-2,4-dienone = 1,2-benzoquinone monoimine
isophenoxazine = 2-aminophenoxazin-3-one
Other name(s): isophenoxazine synthase; o-aminophenol:O2 oxidoreductase; 2-aminophenol:O2 oxidoreductase; GriF
Systematic name: 2-aminophenol:oxygen oxidoreductase
Comments: A flavoprotein. While the enzyme from the plant Tecoma stans is activated by Mn2+ [1], that from the bacterium Streptomyces griseus (GriF) requires Cu2+ for maximal activity. Two molecules of the product 6-iminocyclohexa-2,4-dienone (i.e. 1,2-benzoquinone monoimine) spontaneously condense with oxidation to yield 2-aminophenoxazin-3-one [4]. 3-Amino-4-hydroxybenzaldehyde, which has a -CHO group at the para-position with respect fo the hydroxy group of 2-aminophenol, was found to be the best substrate for GriF [4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9013-85-8
References:
1. Nair, P.M. and Vaidynathan, C.S. Isophenoxazine synthase. Biochim. Biophys. Acta 81 (1964) 507-516.
2. Nair, P.M. and Vining, L.C. Isophenoxazine synthase apoenzyme from Pycnoporus coccineus. Biochim. Biophys. Acta 96 (1965) 318-327. [PMID: 14298835]
3. Subba Rao, P.V. and Vaidyanathan, C.S. Studies on the metabolism of o-aminophenol. Purification and properties of isophenoxazine synthase from Bauhenia monandra. Arch. Biochem. Biophys. 118 (1967) 388-394. [PMID: 4166439]
4. Suzuki, H., Furusho, Y., Higashi, T., Ohnishi, Y. and Horinouchi, S. A novel o-aminophenol oxidase responsible for formation of the phenoxazinone chromophore of grixazone. J. Biol. Chem. 281 (2006) 824-833. [PMID: 16282322]
[EC 1.13.12.11 Deleted entry: methylphenyltetrahydropyridine N-monooxygenase. The activity is due to EC 1.14.13.8, flavin-containing monooxygenase. (EC 1.13.12.11 created 1992, deleted 2006)]
Common name: [histone-H3]-lysine-36 demethylase
Reaction: (1) protein 6-N,6-N-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein 6-N-methyl-L-lysine + succinate + formaldehyde + CO2
(2) protein 6-N-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2
Other name(s): JHDM1A; JmjC domain-containing histone demethylase 1A; H3-K36-specific demethylase; histone-lysine (H3-K36) demethylase; histone demethylase
Systematic name: protein-6-N,6-N-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys-36. Lysine residues exist in three methylation states (mono-, di- and trimethylated). The enzyme preferentially demethylates the dimethyl form of Lys-36 (K36me2), which is its natural substrate, to form the monomethyl and unmethylated forms of Lys-36. It can also demethylate the monomethyl- but not the trimethyl form of Lys-36.
References:
1. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P. and Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439 (2006) 811-816. [PMID: 16362057]
Common name: flavin-containing monooxygenase
Reaction: N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O
Other name(s): dimethylaniline oxidase; dimethylaniline N-oxidase; FAD-containing monooxygenase; N,N-dimethylaniline monooxygenase; DMA oxidase; flavin mixed function oxidase; Ziegler's enzyme; mixed-function amine oxidase; FMO; FMO-I; FMO-II; FMO1; FMO2; FMO3; FMO4; FMO5; flavin monooxygenase; methylphenyltetrahydropyridine N-monooxygenase; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine:oxygen N-oxidoreductase; dimethylaniline monooxygenase (N-oxide-forming)
Systematic name: N,N-dimethylaniline,NADPH:oxygen oxidoreductase (N-oxide-forming)
Comments: A flavoprotein. A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines [3,4]. This enzyme is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate [4,5]. This microsomal enzyme generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [2,6]
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 37256-73-8
References:
1. Ziegler, D.M. and Pettit, F.H. Microsomal oxidases. I. The isolation and dialkylarylamine oxygenase activity of pork liver microsomes. Biochemistry 5 (1966) 2932-2938. [PMID: 4381353]
2. Chiba, K., Kubota, E., Miyakawa, T., Kato, Y. and Ishizaki, T. Characterization of hepatic microsomal metabolism as an in vivo detoxication pathway of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. J. Pharmacol. Exp. Ther. 246 (1988) 1108-1115. [PMID: 3262153]
3. Cashman, J.R. Structural and catalytic properties of the mammalian flavin-containing monooxygenase. Chem. Res. Toxicol. 8 (1995) 165-181.
4. Cashman, J.R. and Zhang, J. Human flavin-containing monooxygenases. Annu. Rev. Pharmacol. Toxicol. 46 (2006) 65-100. [PMID: 16402899]
5. Jones, K.C. and Ballou, D.P. Reactions of the 4a-hydroperoxide of liver microsomal flavin-containing monooxygenase with nucleophilic and electrophilic substrates. J. Biol. Chem. 261 (1986) 2553-2559. [PMID: 3949735]
6. Chiba, K., Kobayashi, K., Itoh, K., Itoh, S., Chiba, T., Ishizaki, T. and Kamataki, T. N-Oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the rat liver flavin-containing monooxygenase expressed in yeast cells. Eur. J. Pharmacol. 293 (1995) 97-100. [PMID: 7672012]
[EC 1.17.1.6 Transferred entry: now EC 1.17.99.5, bile-acid 7α-dehydroxylase. It is now known that FAD is the acceptor and not NAD+ as was thought previously. (EC 1.17.1.6 created 2005, deleted 2006)]
Common name: bile-acid 7α-dehydroxylase
Reaction: (1) deoxycholate + FAD + H2O = cholate + FADH2
(2) lithocholate + FAD + H2O = chenodeoxycholate + FADH2
For diagram click here and mechanism click here.
Glossary: allodeoxycholate = 3α,12α-dihydroxy-5α-cholan-24-oate
cholate = 3α,7α,12α-trihydroxy-5β-cholan-24-oate
chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
deoxycholate = 3α,12α-dihydroxy-5β-cholan-24-oate
lithocholate = 3α-hydroxy-5β-cholan-24-oate
Other name(s): cholate 7α-dehydroxylase; 7α-dehydroxylase; bile acid 7-dehydroxylase; deoxycholate:NAD+ oxidoreductase
Systematic name: deoxycholate:FAD oxidoreductase (7α-dehydroxylating)
Comments: Under physiological conditions, the reactions occur in the reverse direction to that shown above. This enzyme is highly specific for bile-acid substrates and requires a free C-24 carboxy group and an unhindered 7α-hydroxy group on the B-ring of the steroid nucleus for activity, as found in cholate and chenodeoxycholate. The reaction is stimulated by the presence of NAD+ but is inhibited by excess NADH. This unusual regulation by the NAD+/NADH ratio is most likely the result of the intermediates being linked at C-24 by an anhydride bond to the 5'-diphosphate of 3'-phospho-ADP [2,5,6]. Allodeoxycholate is also formed as a side-product of the 7α-dehydroxylation of cholate [6]. The enzyme is present in intestinal anaerobic bacteria [6], even though its products are important in mammalian physiology.
References:
1. White, B.A., Cacciapuoti, A.F., Fricke, R.J., Whitehead, T.R., Mosbach, E.H. and Hylemon, P.B. Cofactor requirements for 7α-dehydroxylation of cholic and chenodeoxycholic acid in cell extracts of the intestinal anaerobic bacterium, Eubacterium species V.P.I. 12708. J. Lipid Res. 22 (1981) 891-898. [PMID: 7276750]
2. White, B.A., Paone, D.A., Cacciapuoti, A.F., Fricke, R.J., Mosbach, E.H. and Hylemon, P.B. Regulation of bile acid 7-dehydroxylase activity by NAD+ and NADH in cell extracts of Eubacterium species V.P.I. 12708. J. Lipid Res. 24 (1983) 20-27. [PMID: 6833878]
3. Coleman, J.P., White, W.B. and Hylemon, P.B. Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain VPI 12708. J. Bacteriol. 169 (1987) 1516-1521. [PMID: 3549693]
4. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]
5. Coleman, J.P., White, W.B., Egestad, B., Sjövall, J. and Hylemon, P.B. Biosynthesis of a novel bile acid nucleotide and mechanism of 7α-dehydroxylation by an intestinal Eubacterium species. J. Biol. Chem. 262 (1987) 4701-4707. [PMID: 3558364]
6. Hylemon, P.B., Melone, P.D., Franklund, C.V., Lund, E. and Björkhem, I. Mechanism of intestinal 7α-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product. J. Lipid Res. 32 (1991) 89-96. [PMID: 2010697]
Common name: globotriaosylceramide 3-β-N-acetylgalactosaminyltransferase
Reaction: UDP-N-acetyl-D-galactosamine + α-D-galactosyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosylceramide = UDP + β-N-acetyl-D-galactosaminyl-(1→3)-α-D-galactosyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosylceramide
Glossary: globotriaosylceramide = Pk antigen = α-D-galactosyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosylceramide
globotetraosylceramide = globoside = P antigen = β-N-acetyl-D-galactosaminyl-(1→3)-α-D-galactosyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosylceramide
Other name(s): uridine diphosphoacetylgalactosamine-galactosylgalactosylglucosylceramide acetylgalactosaminyltransferase; globoside synthetase; UDP-N-acetylgalactosamine:globotriaosylceramide β-3-N-acetylgalactosaminyltransferase; galactosylgalactosylglucosylceramide β-D-acetylgalactosaminyltransferase; UDP-N-acetylgalactosamine:globotriaosylceramide β1,3-N-acetylgalactosaminyltransferase; globoside synthase; galactosylgalactosylglucosylceramide β-D-acetylgalactosaminyltransferase; UDP-N-acetyl-D-galactosamine:D-galactosyl-1,4-D-galactosyl-1,4-D-glucosylceramide β-N-acetyl-D-galactosaminyltransferase; β3GalNAc-T1
Systematic name: UDP-N-acetyl-D-galactosamine:α-D-galactosyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosylceramide 3III-β-N-acetyl-D-galactosaminyltransferase
Comments: Globoside is a neutral glycosphingolipid in human erythrocytes and has blood-group-P-antigen activity [4]. The enzyme requires a divalent cation for activity, with Mn2+ required for maximal activity [3]. UDP-GalNAc is the only sugar donor that is used efficiently by the enzyme: UDP-Gal and UDP-GlcNAc result in very low enzyme activity [3]. Lactosylceramide, globoside and gangliosides GM3 and GD3 are not substrates [4]. For explanation of the superscripted 'III' in the systematic name, see 2-carb.37.
Links to other databases: BRENDA, ERGO, EXPASY, GO, KEGG, CAS registry number: 62213-46-1
References:
1. Chien, J.-L., Williams, T. and Basu, S. Biosynthesis of a globoside-type glycosphingolipid by a β-N-acetylgalactosaminyltransferase from embryonic chicken brain. J. Biol. Chem. 248 (1973) 1778-1785. [PMID: 4632917]
2. Ishibashi, T., Kijimoto, S. and Makita, A. Biosynthesis of globoside and Forssman hapten from trihexosylceramide and properties of β-N-acetyl-galactosaminyltransferase of guinea pig kidney. Biochim. Biophys. Acta 337 (1974) 92-106. [PMID: 4433547]
3. Taniguchi, N. and Makita, A. Purification and characterization of UDP-N-acetylgalactosamine: globotriaosylceramide β-3-N-acetylgalactosaminyltransferase, a synthase of human blood group P antigen, from canine spleen. J. Biol. Chem. 259 (1984) 5637-5642. [PMID: 6425294]
4. Okajima, T., Nakamura, Y., Uchikawa, M., Haslam, D.B., Numata, S.I., Furukawa, K., Urano, T. and Furukawa, K. Expression cloning of human globoside synthase cDNAs. Identification of β3Gal-T3 as UDP-N-acetylgalactosamine:globotriaosylceramide β1,3-N-acetylgalactosaminyltransferase. J. Biol. Chem. 275 (2000) 40498-40503. [PMID: 10993897]
Common name: (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
Reaction: UDP-N-acetyl-D-galactosamine + 1-O-[O-(N-acetyl-α-neuraminosyl)-(2→3)-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide = UDP + 1-O-[O-2-(acetylamino)-2-deoxy-β-D-galactopyranosyl-(1→4)-O-[N-acetyl-α-neuraminosyl-(2→3)]-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
Glossary: ganglioside GM2 = 1-O-[O-2-(acetylamino)-2-deoxy-β-D-galactopyranosyl-(1→4)-O-[N-acetyl-α-neuraminosyl-(2→3)]-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
ganglioside GM3 = 1-O-[O-(N-acetyl-α-neuraminosyl)-(2→3)-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
ganglioside GD3 = 1-O-[O-(N-acetyl-α-neuraminosyl)-(2→8)-O-(N-acetyl-α-neuraminosyl)-(2→3)-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
ganglioside GD2 = 1-O-[O-(N-acetyl-α-neuraminosyl)-(2→8)-O-(N-acetyl-α-neuraminosyl)-(2→3)-O-[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl-(1→4)]-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
ganglioside SM3 = 1-O-[4-O-(3-O-sulfo-β-D-galactopyranosyl)-β-D-glucopyranosyl]-ceramide
ganglioside SM2 = 1-O-[O-2-(acetylamino)-2-deoxy-β-D-galactopyranosyl-(1→4)-O-3-O-sulfo-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide
Other name(s): uridine diphosphoacetylgalactosamine-ganglioside GM3 acetylgalactosaminyltransferase; ganglioside GM2 synthase; ganglioside GM3 acetylgalactosaminyltransferase; GM2 synthase; UDP acetylgalactosamine-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide acetylgalactosaminyltransferase; UDP-N-acetylgalactosamine GM3 N-acetylgalactosaminyltransferase; uridine diphosphoacetylgalactosamine-acetylneuraminylgalactosylglucosylceramide acetylgalactosaminyltransferase; uridine diphosphoacetylgalactosamine-hematoside acetylgalactosaminyltransferase; GM2/GD2-synthase; β-1,4N-aetylgalactosaminyltransferase; asialo-GM2 synthase; GalNAc-T; UDP-N-acetyl-D-galactosamine:(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide N-acetyl-D-galactosaminyltransferase
Systematic name: UDP-N-acetyl-D-galactosamine:1-O-[O-(N-acetyl-α-neuraminosyl)-(2→3)-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide 1,4-β-N-acetyl-D-galactosaminyltransferase
Comments: This enzyme catalyses the formation of the gangliosides (i.e. sialic-acid-containing glycosphingolipids) GM2, GD2 and SM2 from GM3, GD3 and SM3, respectively. Asialo-GM3 [3] and lactosylceramide [2] are also substrates, but glycoproteins and oligosaccharides are not substrates.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 67338-98-1
References:
1. Dicesare, J.L. and Dain, J.A. The enzymic synthesis of ganglioside. IV. UDP-N-acetylgalactosamine: (N-acetylneuraminyl)-galactosylglucosyl ceramide N-acetylgalactosaminyltransferase in rat brain. Biochim. Biophys. Acta 231 (1971) 385-393. [PMID: 5554906]
2. Pohlentz, G., Klein, D., Schwarzmann, G., Schmitz, D. and Sandhoff, K. Both GA2, GM2, and GD2 synthases and GM1b, GD1a, and GT1b synthases are single enzymes in Golgi vesicles from rat liver. Proc. Natl. Acad. Sci. USA 85 (1988) 7044-7048. [PMID: 3140234]
3. Kazuya, I.-P., Hidari, J.K., Ichikawa, S., Furukawa, K., Yamasaki, M. and Hirabayashi, Y. β1-4N-Acetylgalactosaminyltransferase can synthesize both asialoglycosphingolipid GM2 and glycosphingolipid GM2 in vitro and in vivo: isolation and characterization of a β1-4N-acetylgalactosaminyltransferase cDNA clone from rat ascites hepatoma cell line AH7974F. Biochem. J. 303 (1994) 957-965. [PMID: 7980468]
4. Hashimoto, Y., Sekine, M., Iwasaki, K. and Suzuki, A. Purification and characterization of UDP-N-acetylgalactosamine GM3/GD3 N-acetylgalactosaminyltransferase from mouse liver. J. Biol. Chem. 268 (1993) 25857-25864. [PMID: 8245020]
5. Nagai, K. and Ishizuka, I. Biosynthesis of monosulfogangliotriaosylceramide and GM2 by N-acetylgalactosaminyltransferase from rat brain. J. Biochem. (Tokyo) 101 (1987) 1115-1127. [PMID: 3115968]
6. Furukawa, K., Takamiya, K. and Furukawa, K. β1,4-N-Acetylgalactosaminyltransferase—GM2/GD2 synthase: a key enzyme to control the synthesis of brain-enriched complex gangliosides. Biochim. Biophys. Acta 1573 (2002) 356-362. [PMID: 12417418]
7. Yamashita, T., Wu, Y.P., Sandhoff, R., Werth, N., Mizukami, H., Ellis, J.M., Dupree, J.L., Geyer, R., Sandhoff, K. and Proia, R.L. Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions. Proc. Natl. Acad. Sci. USA 102 (2005) 2725-2730. [PMID: 15710896]
Common name: cyanidin 3-O-rutinoside 5-O-glucosyltransferase
Reaction: UDP-glucose + cyanidin 3-O-rutinoside = UDP + cyanidin 3-O-rutinoside 5-O-β-D-glucoside
For diagram click here.
Other name(s): uridine diphosphoglucose-cyanidin 3-rhamnosylglucoside 5-O-glucosyltransferase; cyanidin-3-rhamnosylglucoside 5-O-glucosyltransferase; UDP-glucose:cyanidin-3-O-D-rhamnosyl-1,6-D-glucoside 5-O-D-glucosyltransferase
Systematic name: UDP-glucose:cyanidin-3-O-β-L-rhamnosyl-(1→6)-β-D-glucoside 5-O-β-D-glucosyltransferase
Comments: Also acts on pelargonidin-3-rutinoside. The enzyme does not catalyse the glucosylation of the 5-hydroxy group of cyanidin-3-glucoside.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 70248-66-7
References:
1. Kamsteeg, J., van Brederode, J. and van Nigtevecht, G. Identification, properties, and genetic control of UDP-glucose: cyanidin-3-rhamnosyl-(1→6)-glucoside-5-O-glucosyltransferase isolated from petals of the red campion (Silene dioica). Biochem. Genet. 16 (1978) 1059-1071. [PMID: 751641]
[EC 2.4.1.154 Deleted entry: globotriosylceramide β-1,6-N-acetylgalactosaminyl-transferase. The enzyme is identical to EC 2.4.1.79, globotriaosylceramide 3-β-N-acetylgalactosaminyltransferase. The reference cited referred to a 1→3 linkage and not to a 1→6 linkage, as indicated in the enzyme entry. (EC 2.4.1.154 created 1986, deleted 2006)]
[EC 2.4.1.235 Deleted entry: Enzyme is identical to EC 2.4.1.116, cyanidin 3-O-rutinoside 5-O-glucosyltransferase (EC 2.4.1.235 created 2004, deleted 2006)]
Common name: NAD(P)+—protein-arginine ADP-ribosyltransferase
Reaction: NAD(P)+ + protein L-arginine = nicotinamide + Nω-(ADP-D-ribosyl)-protein-L-arginine
Other name(s): ADP-ribosyltransferase; mono(ADP-ribosyl)transferase; NAD+:L-arginine ADP-D-ribosyltransferase; NAD(P)+-arginine ADP-ribosyltransferase; NAD(P)+-arginine ADP-ribosyltransferase; NAD(P)+:L-arginine ADP-D-ribosyltransferase
Systematic name: NAD(P)+:protein-L-arginine ADP-D-ribosyltransferase
Comments: Arginine residues in proteins act as acceptors. Free arginine, agmatine [(4-aminobutyl)guanidine], arginine methyl ester and guanidine can also do so. The enzyme catalyses the NAD+-dependent activation of EC 4.6.1.1, adenylate cyclase. Some bacterial enterotoxins possess similar enzymatic activities. (cf. EC 2.4.2.36 NAD+—diphthamide ADP-ribosyltransferase).
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 81457-93-4
References:
1. Moss, J., Stanley, S.J. and Oppenheimer, N.J. Substrate specificity and partial purification of a stereospecific NAD- and guanidine-dependent ADP-ribosyltransferase from avian erythrocytes. J. Biol. Chem. 254 (1979) 8891-8894. [PMID: 225315]
2. Moss, J., Stanley, S.J. and Watkins, P.A. Isolation and properties of an NAD- and guanidine-dependent ADP-ribosyltransferase from turkey erythrocytes. J. Biol. Chem. 255 (1980) 5838-5840. [PMID: 6247348]
3. Ueda, K. and Hayaishi, O. ADP-ribosylation. Annu. Rev. Biochem. 54 (1985) 73-100. [PMID: 3927821]
Common name: putrescine aminotransferase
Reaction: (1) putrescine + 2-oxoglutarate = 4-aminobutanal + L-glutamate
(2) 4-aminobutanal = 1-pyrroline (spontaneous)
For diagram click here.
Glossary: putrescine = butane-1,4-diamine
1-pyrroline = 3,4-dihydro-2H-pyrrole
Other name(s): putrescine-α-ketoglutarate transaminase; YgjG; putrescine:α-ketoglutarate aminotransferase; PAT; putrescine:2-oxoglutarate aminotransferase; putrescine transaminase
Systematic name: butane-1,4-diamine:2-oxoglutarate aminotransferase
Comments: A pyridoxal-phosphate protein [3]. The product, 4-aminobutanal, spontaneously cyclizes to form 1-pyrroline, which is a substrate for EC 1.5.1.35, 1-pyrroline dehydrogenase. Cadaverine and spermidine can also act as substrates [3]. Forms part of the arginine-catabolism pathway [2].
References:
1. Prieto-Santos, M.I., Martin-Checa, J., Balaña-Fouce, R. and Garrido-Pertierra, A. A pathway for putrescine catabolism in Escherichia coli. Biochim. Biophys. Acta 880 (1986) 242-244. [PMID: 3510672]
2. Samsonova, N.N., Smirnov, S.V., Novikova, A.E. and Ptitsyn, L.R. Identification of Escherichia coli K12 YdcW protein as a γ-aminobutyraldehyde dehydrogenase. FEBS Lett. 579 (2005) 4107-4112. [PMID: 16023116]
3. Samsonova, N.N., Smirnov, S.V., Altman, I.B. and Ptitsyn, L.R. Molecular cloning and characterization of Escherichia coli K12 ygjG gene. BMC Microbiol. 3 (2003) 2 only. [PMID: 12617754]
Common name: LL-diaminopimelate aminotransferase
Reaction: LL-2,6-diaminoheptanedioate + 2-oxoglutarate = (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + L-glutamate + H2O
For diagram click here.
Glossary: LL-diaminopimelate = LL-2,6-diaminoheptanedioate
tetrahydrodipicolinate = 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate
Other name(s): LL-diaminopimelate transaminase; LL-DAP aminotransferase; LL-DAP-AT
Systematic name: LL-2,6-diaminoheptanedioate:2-oxoglutarate aminotransferase
Comments: A pyridoxal-phosphate enzyme. In vivo, the reaction occurs in the opposite direction to that shown above. This is one of the final steps in the lysine-biosynthesis pathway of plants (ranging from mosses to flowering plants). meso-Diaminoheptanedioate, an isomer of LL-2,6-diaminoheptanedioate, and the structurally related compounds lysine and ornithine are not substrates. 2-Oxoglutarate cannot be replaced by oxaloacetate or pyruvate. It is not yet known if the substrate of the biosynthetic reaction is the cyclic or acyclic form of tetrahydropyridine-2,6-dicarboxylate.
References:
1. Hudson, A.O., Singh, B.K., Leustek, T. and Gilvarg, C. An LL-diaminopimelate aminotransferase defines a novel variant of the lysine biosynthesis pathway in plants. Plant Physiol. 140 (2006) 292-301. [PMID: 16361515]
Common name: 2'-phosphotransferase
Reaction: 2'-phospho-[ligated tRNA] + NAD+ = mature tRNA + ADP ribose 1",2"-phosphate + H2O
For diagram click here and for mechanism, click here.
Glossary: ADP-ribose = adenosine 5'-(5-deoxy-D-ribofuranos-5-yl diphosphate)
Other name(s): yeast 2'-phosphotransferase; Tpt1; Tpt1p; 2'-phospho-tRNA:NAD+ phosphotransferase
Systematic name: 2'-phospho-[ligated tRNA]:NAD+ phosphotransferase
Comments: Catalyses the final step of tRNA splicing in the yeast Saccharomyces cerevisiae [2]. The reaction takes place in two steps: in the first step, the 2'-phosphate on the RNA substrate is ADP-ribosylated, causing the relase of nicotinamide and the formation of the reaction intermediate, ADP-ribosylated tRNA [6]. In the second step, dephosphorylated (mature) tRNA is formed along with ADP ribose 1",2"-cyclic phosphate. Highly specific for oligonucleotide substrates bearing an internal 2'-phosphate. Oligonucleotides with only a terminal 5'- or 3'-phosphate are not substrates [1].
References:
1. Steiger, M.A., Kierzek, R., Turner, D.H. and Phizicky, E.M. Substrate recognition by a yeast 2'-phosphotransferase involved in tRNA splicing and by its Escherichia coli homolog. Biochemistry 40 (2001) 14098-14105. [PMID: 11705403]
2. Spinelli, S.L., Kierzek, R., Turner, D.H. and Phizicky, E.M. Transient ADP-ribosylation of a 2'-phosphate implicated in its removal from ligated tRNA during splicing in yeast. J. Biol. Chem. 274 (1999) 2637-2644. [PMID: 9915792]
3. Culver, G.M., McCraith, S.M., Consaul, S.A., Stanford, D.R. and Phizicky, E.M. A 2'-phosphotransferase implicated in tRNA splicing is essential in Saccharomyces cerevisiae. J. Biol. Chem. 272 (1997) 13203-13210. [PMID: 9148937]
4. McCraith, S.M. and Phizicky, E.M. An enzyme from Saccharomyces cerevisiae uses NAD+ to transfer the splice junction 2'-phosphate from ligated tRNA to an acceptor molecule. J. Biol. Chem. 266 (1991) 11986-11992. [PMID: 2050693]
5. Hu, Q.D., Lu, H., Huo, K., Ying, K., Li, J., Xie, Y., Mao, Y. and Li, Y.Y. A human homolog of the yeast gene encoding tRNA 2'-phosphotransferase: cloning, characterization and complementation analysis. Cell. Mol. Life Sci. 60 (2003) 1725-1732. [PMID: 14504659]
6. Steiger, M.A., Jackman, J.E. and Phizicky, E.M. Analysis of 2'-phosphotransferase (Tpt1p) from Saccharomyces cerevisiae: evidence for a conserved two-step reaction mechanism. RNA 11 (2005) 99-106. [PMID: 15611300]
7. Sawaya, R., Schwer, B. and Shuman, S. Structure-function analysis of the yeast NAD+-dependent tRNA 2'-phosphotransferase Tpt1. RNA 11 (2005) 107-113. [PMID: 15611301]
8. Kato-Murayama, M., Bessho, Y., Shirouzu, M. and Yokoyama, S. Crystal structure of the RNA 2'-phosphotransferase from Aeropyrum pernix K1. J. Mol. Biol. 348 (2005) 295-305. [PMID: 15811369]
Common name: ribose 1,5-bisphosphate phosphokinase
Reaction: ATP + ribose 1,5-bisphosphate = ADP + 5-phospho-α-D-ribose 1-diphosphate
Glossary: PRPP = 5-phospho-α-D-ribose 1-diphosphate
Other name(s): ribose 1,5-bisphosphokinase; PhnN
Systematic name: ATP:ribose-1,5-bisphosphate phosphotransferase
Comments: This enzyme, found in NAD supression mutants of Escherichia coli, synthesizes 5-phospho-α-D-ribose 1-diphosphate (PRPP) without the participation of EC 2.7.6.1, ribose-phosphate diphosphokinase. Ribose, ribose 1-phosphate and ribose 5-phosphate are not substrates, and GTP cannot act as a phosphate donor.
References:
1. Hove-Jensen, B., Rosenkrantz, T.J., Haldimann, A. and Wanner, B.L. Escherichia coli phnN, encoding ribose 1,5-bisphosphokinase activity (phosphoribosyl diphosphate forming): dual role in phosphonate degradation and NAD biosynthesis pathways. J. Bacteriol. 185 (2003) 2793-2801. [PMID: 12700258]
Common name: holo-[acyl-carrier-protein] synthase
Reaction: CoA-[4'-phosphopantetheine] + apo-[acyl-carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-carrier-protein]
Other name(s): acyl carrier protein holoprotein (holo-ACP) synthetase; holo-ACP synthetase; coenzyme A:fatty acid synthetase apoenzyme 4'-phosphopantetheine transferase; holosynthase; acyl carrier protein synthetase; holo-ACP synthase; PPTase; AcpS; ACPS; acyl carrier protein synthase; P-pant transferase; CoA:apo-[acyl-carrier-protein] pantetheinephosphotransferase
Systematic name: CoA-[4'-phosphopantetheine]:apo-[acyl-carrier-protein] 4'-pantetheinephosphotransferase
Comments: Requires Mg2+. All polyketide synthases, fatty-acid synthases and non-ribosomal peptide synthases require post-translational modification of their constituent acyl-carrier-protein (ACP) domains to become catalytically active. The inactive apo-proteins are converted into their active holo-forms by transfer of the 4'-phosphopantetheinyl moiety of CoA to the sidechain hydroxy group of a conserved serine residue in each ACP domain [3]. The enzyme from human can activate both the ACP domain of the human cytosolic multifunctional fatty acid synthase and that associated with human mitochondria as well as peptidyl-carrier and acyl-carrier-proteins from prokaryotes [6]. Removal of the 4-phosphopantetheinyl moiety from holo-ACP is carried out by EC 3.1.4.14, [acyl-carrier-protein] phosphodiesterase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 37278-30-1
References:
1. Elovson, J. and Vagelos, P.R. Acyl carrier protein. X. Acyl carrier protein synthetase. J. Biol. Chem. 243 (1968) 3603-3611. [PMID: 4872726]
2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269-311. [PMID: 4561013]
3. Lambalot, R.H., Gehring, A.M., Flugel, R.S., Zuber, P., LaCelle, M., Marahiel, M.A., Reid, R., Khosla, C. and Walsh, C.T. A new enzyme superfamily - the phosphopantetheinyl transferases. Chem. Biol. 3 (1996) 923-936. [PMID: 8939709]
4. Walsh, C.T., Gehring, A.M., Weinreb, P.H., Quadri, L.E.N. and Flugel, R.S. Post-translational modification of polyketide and nonribosomal peptide synthases. Curr. Opin. Chem. Biol. 1 (1997) 309-315. [PMID: 9667867]
5. Mootz, H.D., Finking, R. and Marahiel, M.A. 4'-Phosphopantetheine transfer in primary and secondary metabolism of Bacillus subtilis. J. Biol. Chem. 276 (2001) 37289-37298. [PMID: 11489886]
6. Joshi, A.K., Zhang, L., Rangan, V.S. and Smith, S. Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. J. Biol. Chem. 278 (2003) 33142-33149. [PMID: 12815048]
Common name: acetylajmaline esterase
Reaction: (1) 17-O-acetylajmaline + H2O = ajmaline + acetate
(2) 17-O-acetylnorajmaline + H2O = norajmaline + acetate
For diagram click here.
Other name(s): acetylajmalan esterase; AAE; 2β(R)-17-O-acetylajmalan:acetylesterase
Systematic name: 17-O-acetylajmaline O-acetylhydrolase
Comments: This plant enzyme is responsible for the last stages in the biosynthesis of the indole alkaloid ajmaline. The enzyme is highly specific for the substrates 17-O-acetylajmaline and 17-O-acetylnorajmaline as the structurally related acetylated alkaloids vinorine, vomilenine, 1,2-dihydrovomilenine and 1,2-dihydroraucaffricine cannot act as substrates [2]. This is a novel member of the GDSL family of serine esterases/lipases.
References:
1. Polz, L., Schübel, H. and Stöckigt, J. Characterization of 2β(R)-17-O-acetylajmalan:acetylesterase—a specific enzyme involved in the biosynthesis of the Rauwolfia alkaloid ajmaline. Z. Naturforsch. [C] 42 (1987) 333-342. [PMID: 2955586]
2. Ruppert, M., Woll, J., Giritch, A., Genady, E., Ma, X. and Stöckigt, J. Functional expression of an ajmaline pathway-specific esterase from Rauvolfia in a novel plant-virus expression system. Planta 222 (2005) 888-898. [PMID: 16133216]
Common name: acireductone synthase
Reaction: 5-(methylthio)-2,3-dioxopentyl phosphate + H2O = 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + phosphate
(1a) 5-(methylthio)-2,3-dioxopentyl phosphate = 2-hydroxy-5-(methylthio)-3-oxopent-1-enyl phosphate
(1b) 2-hydroxy-5-(methylthio)-3-oxopent-1-enyl phosphate + H2O = 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + phosphate
For diagram click here.
Glossary: acireductone = 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one
Other name(s): E1; E-1 enolase-phosphatase
Systematic name: 5-(methylthio)-2,3-dioxopentyl-phosphate phosphohydrolase (isomerizing)
Comments: This bifunctional enzyme first enolizes the substrate to form the intermediate 2-hydroxy-5-(methylthio)-3-oxopent-1-enyl phosphate, which is then dephosphorylated to form the acireductone 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one [2]. The acireductone represents a branch point in the methione-salvage pathway as it is used in the formation of formate, CO and 3-(methylthio)propanoate by EC 1.13.11.53 [acireductone dioxygenase (Ni2+-requiring)] and of formate and 4-methylthio-2-oxobutanoate either by a spontaneous reaction under aerobic conditions or by EC 1.13.11.54 {acireductone dioxygenase [iron(II)-requiring]} [1,2].
References:
1. Myers, R.W., Wray, J.W., Fish, S. and Abeles, R.H. Purification and characterization of an enzyme involved in oxidative carbon-carbon bond cleavage reactions in the methionine salvage pathway of Klebsiella pneumoniae. J. Biol. Chem. 268 (1993) 24785-24791. [PMID: 8227039]
2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in Klebsiella pneumoniae and rat liver. Identification and characterization of two novel dioxygenases. J. Biol. Chem. 270 (1995) 3147-3153. [PMID: 7852397]
Common name: [acyl-carrier-protein] phosphodiesterase
Reaction: holo-[acyl-carrier-protein] + H2O = 4'-phosphopantetheine + apo-[acyl-carrier-protein]
Other name(s): ACP hydrolyase; ACP phosphodiesterase; AcpH; [acyl-carrier-protein] 4'-pantetheine-phosphohydrolase
Systematic name: holo-[acyl-carrier-protein] 4'-pantetheine-phosphohydrolase
Comments: The enzyme cleaves acyl-[acyl-carrier-protein] species with acyl chains of 6-16 carbon atoms although it appears to demonstrate a preference for the unacylated acyl-carrier-protein (ACP) and short-chain ACPs over the medium- and long-chain species [3]. Deletion of the gene encoding this enzyme abolishes ACP prosthetic-group turnover in vivo [3]. Activation of apo-ACP to form the holoenzyme is carried out by EC 2.7.8.7, holo-[acyl-carrier-protein] synthase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 37288-21-4
References:
1. Sobhy, C. Regulation of fatty acid synthetase activity. The 4'-phosphopantetheine hydrolase of rat liver. J. Biol. Chem. 254 (1979) 8561-8566. [PMID: 224058]
2. Vagelos, P.R. and Larrabee, A.R. Acyl carrier protein. IX. Acyl carrier protein hydrolase. J. Biol. Chem. 242 (1967) 1776-1781. [PMID: 4290442]
3. Thomas, J. and Cronan, J.E. The enigmatic acyl carrier protein phosphodiesterase of Escherichia coli: genetic and enzymological characterization. J. Biol. Chem. 280 (2005) 34675-34683. [PMID: 16107329]
Common name: purine nucleosidase
Reaction: a purine nucleoside + H2O = D-ribose + a purine base
Other name(s): nucleosidase; purine β-ribosidase; purine nucleoside hydrolase; purine ribonucleosidase; ribonucleoside hydrolase; nucleoside hydrolase; N-ribosyl purine ribohydrolase; nucleosidase g; N-D-ribosylpurine ribohydrolase; inosine-adenosine-guanosine preferring nucleoside hydrolase; purine-specific nucleoside N-ribohydrolase; IAG-nucleoside hydrolase; IAG-NH
Systematic name: purine-nucleoside ribohydrolase
Comments: The enzyme from the bacterium Ochrobactrum anthropi specifically catalyses the irreversible N-riboside hydrolysis of purine nucleosides. Pyrimidine nucleosides, purine and pyrimidine nucleotides, NAD+, NADP+ and nicotinaminde mononucleotide are not substrates [6].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 9025-44-9
References:
1. Heppel, L.A. and Hilmoe, R.J. Phosphorolysis and hydrolysis of purine ribosides from yeast. J. Biol. Chem. 198 (1952) 683-694. [PMID: 12999785]
2. Kalckar, H.M. Biosynthetic aspects of nucleosides and nucleic acids. Pubbl. Staz. Zool. (Napoli) (1951) 87-103.
3. Takagi, Y. and Horecker, B.L. Purification and properties of a bacterial riboside hydrolyase. J. Biol. Chem. 225 (1956) 77-86.
4. Tarr, H.L.A. Fish muscle riboside hydrolases. Biochem. J. 59 (1955) 386-391.
5. Parkin, D.W. Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism. J. Biol. Chem. 271 (1996) 21713-21719. [PMID: 8702965]
6. Ogawa, J., Takeda, S., Xie, S.X., Hatanaka, H., Ashikari, T., Amachi, T. and Shimizu, S. Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi. Appl. Environ. Microbiol. 67 (2001) 1783-1787. [PMID: 11282633]
7. Versées, W., Decanniere, K., Van Holsbeke, E., Devroede, N. and Steyaert, J. Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax. J. Biol. Chem. 277 (2002) 15938-15946. [PMID: 11854281]
8. Mazumder-Shivakumar, D. and Bruice, T.C. Computational study of IAG-nucleoside hydrolase: determination of the preferred ground state conformation and the role of active site residues. Biochemistry 44 (2005) 7805-7817. [PMID: 15909995]
Common name: methylthioribulose 1-phosphate dehydratase
Reaction: S-methyl-5-thio-D-ribulose 1-phosphate = 5-(methylthio)-2,3-dioxopentyl phosphate + H2O
For diagram click here.
Other name(s): 1-PMT-ribulose dehydratase
Systematic name: S-methyl-5-thio-D-ribulose-1-phosphate hydro-lyase
Comments: This enzyme forms part of the methionine-salvage pathway.
References:
1. Furfine, E.S. and Abeles, R.H. Intermediates in the conversion of 5'-S-methylthioadenosine to methionine in Klebsiella pneumoniae. J. Biol. Chem. 263 (1988) 9598-9606. [PMID: 2838472]
2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in Klebsiella pneumoniae and rat liver. Identification and characterization of two novel dioxygenases. J. Biol. Chem. 270 (1995) 3147-3153. [PMID: 7852397]
[EC 4.2.2.4 Transferred entry: chondroitin ABC lyase. Now known to comprise two enzymes: EC 4.2.2.20, chondroitin-sulfate-ABC endolyase and EC 4.2.2.21, chondroitin-sulfate-ABC exolyase. (EC 4.2.2.4 created 1972 (EC 4.2.99.6 created 1965, part incorporated 1976), deleted 2006)]
Common name: chondroitin-sulfate-ABC endolyase
Reaction: Endolytic cleavage of β-1,4-galactosaminic bonds between N-acetylgalactosamine and either D-glucuronic acid or L-iduronic acid to produce a mixture of Δ4-unsaturated oligosaccharides of different sizes that are ultimately degraded to Δ4-unsaturated tetra- and disaccharides
For diagram click here.
Glossary: chondroitin sulfate A = chondroitin 4-sulfate
chondroitin sulfate B = dermatan sulfate
chondroitin sulfate C = chondroitin 6-sulfate
For the nomenclature of glycoproteins, glycopeptides and peptidoglycans, click here
Other name(s): chondroitinase (ambiguous); chondroitin ABC eliminase (ambiguous); chondroitinase ABC (ambiguous); chondroitin ABC lyase (ambiguous); chondroitin sulfate ABC lyase (ambiguous); ChS ABC lyase (ambiguous); chondroitin sulfate ABC endoeliminase; chondroitin sulfate ABC endolyase; ChS ABC lyase I
Systematic name: chondroitin-sulfate-ABC endolyase
Comments: This enzyme degrades a variety of glycosaminoglycans of the chondroitin-sulfate- and dermatan-sulfate type. Chondroitin sulfate, chondroitin-sulfate proteoglycan and dermatan sulfate are the best substrates but the enzyme can also act on hyaluronan at a much lower rate. Keratan sulfate, heparan sulfate and heparin are not substrates. In general, chondroitin sulfate (CS) and dermatan sulfate (DS) chains comprise a linkage region, a chain cap and a repeat region. The repeat region of CS is a repeating disaccharide of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc) [-4)GlcA(β1-3)GalNAc(β1-]n, which may be O-sulfated on the C-4 and/or C-6 of GalNAc and C-2 of GlcA. GlcA residues of CS may be epimerized to iduronic acid (IdoA) forming the repeating disaccharide [-4)IdoA(α1-3)GalNAc(β1-]n of DS. Both the concentrations and locations of sulfate-ester substituents vary with glucosaminoglycan source [5]. The related enzyme EC 4.2.2.21, chondroitin-sulfate-ABC exolyase, has the same substrate specificity but removes disaccharide residues from the non-reducing ends of both polymeric chondroitin sulfates and their oligosaccharide fragments produced by EC 4.2.2.20 [4].
References:
1. Yamagata, T., Saito, H., Habuchi, O. and Suzuki, S. Purification and properties of bacterial chondroitinases and chondrosulfatases. J. Biol. Chem. 243 (1968) 1523-1535. [PMID: 5647268]
2. Saito, H., Yamagata, T. and Suzuki, S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J. Biol. Chem. 243 (1968) 1536-1542. [PMID: 4231029]
3. Suzuki, S., Saito, H., Yamagata, T., Anno, K., Seno, N., Kawai, Y. and Furuhashi, T. Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion. J. Biol. Chem. 243 (1968) 1543-1550. [PMID: 5647269]
4. Hamai, A., Hashimoto, N., Mochizuki, H., Kato, F., Makiguchi, Y., Horie, K. and Suzuki, S. Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. J. Biol. Chem. 272 (1997) 9123-9130. [PMID: 9083041]
5. Huckerby, T.N., Nieduszynski, I.A., Giannopoulos, M., Weeks, S.D., Sadler, I.H. and Lauder, R.M. Characterization of oligosaccharides from the chondroitin/dermatan sulfates. 1H-NMR and 13C-NMR studies of reduced trisaccharides and hexasaccharides. FEBS J. 272 (2005) 6276-6286. [PMID: 16336265]
Common name: chondroitin-sulfate-ABC exolyase
Reaction: Exolytic cleavage of disaccharide residues from the non-reducing ends of both polymeric chondroitin sulfates and their oligosaccharide fragments
For diagram click here.
Glossary: chondroitin sulfate A = chondroitin 4-sulfate
chondroitin sulfate B = dermatan sulfate
chondroitin sulfate C = chondroitin 6-sulfate
For the nomenclature of glycoproteins, glycopeptides and peptidoglycans, click here
Other name(s): chondroitinase (ambiguous); chondroitin ABC eliminase (ambiguous); chondroitinase ABC (ambiguous); chondroitin ABC lyase (ambiguous); chondroitin sulfate ABC lyase (ambiguous); ChS ABC lyase (ambiguous); chondroitin sulfate ABC exoeliminase; chondroitin sulfate ABC exolyase; ChS ABC lyase II
Systematic name: chondroitin-sulfate-ABC exolyase
Comments: This enzyme degrades a variety of glycosaminoglycans of the chondroitin-sulfate- and dermatan-sulfate type. Chondroitin sulfate, chondroitin-sulfate proteoglycan and dermatan sulfate are the best substrates but the enzyme can also act on hyaluronan at a much lower rate. Keratan sulfate, heparan sulfate and heparin are not substrates. In general, chondroitin sulfate (CS) and dermatan sulfate (DS) chains comprise a linkage region, a chain cap and a repeat region. The repeat region of CS is a repeating disaccharide of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc) [-4)GlcA(β1-3)GalNAc(β1-]n, which may be O-sulfated on the C-4 and/or C-6 of GalNAc and C-2 of GlcA. GlcA residues of CS may be epimerized to iduronic acid (IdoA) forming the repeating disaccharide [-4)IdoA(α1-3)GalNAc(β1-]n of DS. Both the concentrations and locations of sulfate-ester substituents vary with glucosaminoglycan source [5]. The related enzyme EC 4.2.2.20, chondroitin-sulfate-ABC endolyase, has the same substrate specificity but produces a mixture of Δ4-unsaturated oligosaccharides of different sizes that are ultimately degraded to Δ4-unsaturated tetra- and disaccharides [4].
References:
1. Yamagata, T., Saito, H., Habuchi, O. and Suzuki, S. Purification and properties of bacterial chondroitinases and chondrosulfatases. J. Biol. Chem. 243 (1968) 1523-1535. [PMID: 5647268]
2. Saito, H., Yamagata, T. and Suzuki, S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J. Biol. Chem. 243 (1968) 1536-1542. [PMID: 4231029]
3. Suzuki, S., Saito, H., Yamagata, T., Anno, K., Seno, N., Kawai, Y. and Furuhashi, T. Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion. J. Biol. Chem. 243 (1968) 1543-1550. [PMID: 5647269]
4. Hamai, A., Hashimoto, N., Mochizuki, H., Kato, F., Makiguchi, Y., Horie, K. and Suzuki, S. Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. J. Biol. Chem. 272 (1997) 9123-9130. [PMID: 9083041]
5. Huckerby, T.N., Nieduszynski, I.A., Giannopoulos, M., Weeks, S.D., Sadler, I.H. and Lauder, R.M. Characterization of oligosaccharides from the chondroitin/dermatan sulfates. 1H-NMR and 13C-NMR studies of reduced trisaccharides and hexasaccharides. FEBS J. 272 (2005) 6276-6286. [PMID: 16336265]
Common name: L-amino-acid α-ligase
Reaction: ATP + an L-amino acid + an L-amino acid = ADP + phosphate + L-aminoacyl-L-amino acid
Other name(s): L-amino acid α-ligase; bacilysin synthetase; YwfE; L-amino acid ligase
Systematic name: [L-amino acid:L-amino acid ligase (ADP-forming)]
Comments: The enzyme from Bacillus sp. requires Mg2+ or Mn2+ for activity. While the enzyme has extremely broad substrate specificity, it does not accept highly charged amino acids, such as Lys, Arg, Glu and Asp, nor does it react with secondary amines such as Pro. The N-terminal residue of the α-dipeptide formed seems to be limited to Ala, Gly, Ser, Thr and Met (with Ala and Ser being the most preferred), whereas the C-terminal residue seems to allow for a wider variety of amino acids (but with a preference for Met and Phe). However, not all combinations or dipeptides are formed. For example, while Ser is acceptable for the N-terminus and Thr for the C-terminus, a Ser-Thr dipeptide is not formed. D-Ala, D-Ser and D-Phe are not substrates. Belongs in the ATP-dependent carboxylate-amine/thiol ligase superfamily.
References:
1. Tabata, K., Ikeda, H. and Hashimoto, S. ywfE in Bacillus subtilis codes for a novel enzyme, L-amino acid ligase. J. Bacteriol. 187 (2005) 5195-5202. [PMID: 16030213]
Common name: asparagine synthase (glutamine-hydrolysing)
Reaction: ATP + L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine + L-glutamate
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine
Other name(s): asparagine synthetase (glutamine-hydrolysing); glutamine-dependent asparagine synthetase; asparagine synthetase B; AS; AS-B
Systematic name: L-aspartate:L-glutamine amido-ligase (AMP-forming)
Comments: The enzyme from Escherichia coli has two active sites [4] that are connected by an intramolecular ammonia tunnel [6,7]. The enzyme catalyses three distinct chemical reactions: glutamine hydrolysis to yield ammonia takes place in the N-terminal domain. The C-terminal active site mediates both the synthesis of a β-aspartyl-AMP intermediate and its subsequent reaction with ammonia. The ammonia released is channeled to the other active site to yield asparagine [7].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 37318-72-2
References:
1. Patterson, M.K., Jr. and Orr, G.R. Asparagine biosynthesis by the Novikoff hepatoma. Isolation, purification, property, and mechanism studies of the enzyme system. J. Biol. Chem. 243 (1968) 376-380. [PMID: 4295091]
2. Boehlein, S.K., Richards, N.G. and Schuster, S.M. Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. J. Biol. Chem. 269 (1994) 7450-7457. [PMID: 7907328]
3. Richards, N.G. and Schuster, S.M. Mechanistic issues in asparagine synthetase catalysis. Adv. Enzymol. Relat. Areas Mol. Biol. 72 (1998) 145-198. [PMID: 9559053]
4. Larsen, T.M., Boehlein, S.K., Schuster, S.M., Richards, N.G., Thoden, J.B., Holden, H.M. and Rayment, I. Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry 38 (1999) 16146-16157. [PMID: 10587437]
5. Larsen, T.M., Boehlein, S.K., Schuster, S.M., Richards, N.G., Thoden, J.B., Holden, H.M. and Rayment, I. Erratum to: Three-dimensional structure of escherichia coli asparagine synthetase B: A short journey from substrate to product. Biochemistry 39 (2000) 7330 only. [PMID: 10852734]
6. Huang, X., Holden, H.M. and Raushel, F.M. Channeling of substrates and intermediates in enzyme-catalyzed reactions. Annu. Rev. Biochem. 70 (2001) 149-180. [PMID: 11395405]
7. Tesson, A.R., Soper, T.S., Ciustea, M. and Richards, N.G. Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli. Arch. Biochem. Biophys. 413 (2003) 23-31. [PMID: 12706338]
Common name: carbamoyl-phosphate synthase (glutamine-hydrolysing)
Reaction: 2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) 2 ATP + HCO3- = 2 ADP + phosphate + carbamoyl phosphate
For diagram click here.
Other name(s): carbamoyl-phosphate synthetase (glutamine-hydrolysing); carbamyl phosphate synthetase (glutamine); carbamoylphosphate synthetase II; glutamine-dependent carbamyl phosphate synthetase; carbamoyl phosphate synthetase; CPS; carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Systematic name: hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Comments: The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 Å in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxy phosphate to produce the carbamate intermediate. The carboxy-phosphate intermediate is formed by the phosphorylation of bicarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 37233-48-0
References:
1. Anderson, P.M. and Meister, A. Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase. Biochemistry 4 (1965) 2803-2809.
2. Kalman, S.M., Duffield, P.H. and Brzozowski, T. Purification and properties of a bacterial carbamyl phosphate synthetase. J. Biol. Chem. 241 (1966) 1871-1877. [PMID: 5329589]
3. Yip, M.C.M. and Knox, W.E. Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues. J. Biol. Chem. 245 (1970) 2199-2204. [PMID: 5442268]
4. Stapleton, M.A., Javid-Majd, F., Harmon, M.F., Hanks, B.A., Grahmann, J.L., Mullins, L.S. and Raushel, F.M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry 35 (1996) 14352-14361. [PMID: 8916922]
5. Holden, H.M., Thoden, J.B. and Raushel, F.M. Carbamoyl phosphate synthetase: a tunnel runs through it. Curr. Opin. Struct. Biol. 8 (1998) 679-685. [PMID: 9914247]
6. Raushel, F.M., Thoden, J.B., Reinhart, G.D. and Holden, H.M. Carbamoyl phosphate synthetase: a crooked path from substrates to products. Curr. Opin. Chem. Biol. 2 (1998) 624-632. [PMID: 9818189]
7. Raushel, F.M., Thoden, J.B. and Holden, H.M. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry 38 (1999) 7891-7899. [PMID: 10387030]
8. Thoden, J.B., Huang, X., Raushel, F.M. and Holden, H.M. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J. Biol. Chem. 277 (2002) 39722-39727. [PMID: 12130656]