An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
See also entries in separate files for EC 1, EC 3 and EC 4 to EC 6.
Common name: aminomethyltransferase
Reaction: [protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = protein-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
For diagram, click here
Glossary: dihydrolipoyl group
Other name(s): S-aminomethyldihydrolipoylprotein:(6S)-tetrahydrofolate aminomethyltransferase (ammonia-forming); T-protein; glycine synthase; tetrahydrofolate aminomethyltransferase
Systematic name: [protein]-S8-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-forming)
Comments: A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3]
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 37257-08-2
References:
1. Okamura-Ikeda, J., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken liver T protein, a component of the glycine cleavage system. J. Biol. Chem. 257 (1982) 135-139.
2. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961-1004. [PMID: 10966480]
3. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269-282. [PMID: 15642479]
Common name: thioethanolamine S-acetyltransferase
Reaction: acetyl-CoA + 2-aminoethanethiol = CoA + S-(2-aminoethyl)thioacetate
Other name(s): thioltransacetylase B; thioethanolamine acetyltransferase; acetyl-CoA:thioethanolamine S-acetyltransferase
Systematic name: acetyl-CoA:2-aminoethanethiol S-acetyltransferase
Comments: 2-Sulfanylethanol (2-mercaptoethanol) can act as a substrate [1].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9029-93-0
References:
1. Brady, R.O. and Stadtman, E.R. Enzymatic thioltransacetylation. J. Biol. Chem. 211 (1954) 621-629. [PMID: 13221570]
2. Gunsalus, I.C. Group transfer and acyl-generating functions of lipoic acid derivatives. In: McElroy, W.D. and Glass, B. (Ed.), A Symposium on the Mechanism of Enzyme Action, vol. , Johns Hopkins Press, Baltimore, 1954, pp. 545-580.
Common name: [acyl-carrier-protein] S-acetyltransferase
Reaction: acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier-protein]
Other name(s): acetyl coenzyme A-acyl-carrier-protein transacylase; [acyl-carrier-protein]acetyltransferase; [ACP]acetyltransferase; ACAT
Systematic name: acetyl-CoA:[acyl-carrier-protein] S-acetyltransferase
Comments: This enzyme, along with EC 2.3.1.39, [acyl-carrier-protein] S-malonyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. The substrate acetyl-CoA protects the enzyme against inhibition by N-ethylmaleimide or iodoacetamide [4]. This is one of the activities associated with β-ketoacyl-ACP synthase III (EC 2.3.1.180) [5].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 37257-16-2
References:
1. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269-311. [PMID: 4561013]
2. Vance, D.E., Mituhashi, O. and Bloch, K. Purification and properties of the fatty acid synthetase from Mycobacterium phlei. J. Biol. Chem. 248 (1973) 2303-2309. [PMID: 4698221]
3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases. J. Biol. Chem. 241 (1966) 2326-2332. [PMID: 5330116]
4. Lowe, P.N. and Rhodes, S. Purification and characterization of [acyl-carrier-protein] acetyltransferase from Escherichia coli. Biochem. J. 250 (1988) 789-796. [PMID: 3291856]
5. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of the β-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem. 267 (1992) 6807-6814. [PMID: 1551888]
6. Rangan, V.S. and Smith, S. Alteration of the substrate specificity of the malonyl-CoA/acetyl-CoA:acyl carrier protein S-acyltransferase domain of the multifunctional fatty acid synthase by mutation of a single arginine residue. J. Biol. Chem. 272 (1997) 11975-11978. [PMID: 9115261]
Common name: [acyl-carrier-protein] S-malonyltransferase
Reaction: malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier-protein]
Other name(s): malonyl coenzyme A-acyl carrier protein transacylase; malonyl transacylase; malonyl transferase; malonyl-CoA-acyl carrier protein transacylase; [acyl carrier protein]malonyltransferase; MAT; FabD; malonyl-CoA:acyl carrier protein transacylase; malonyl-CoA:ACP transacylase; MCAT; malonyl-CoA:AcpM transacylase
Systematic name: malonyl-CoA:[acyl-carrier-protein] S-malonyltransferase
Comments: This enzyme, along with EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for polyketide biosynthesis [7]. The product of the reaction, malonyl-ACP, is an elongation substrate in fatty-acid biosynthesis. In Mycobacterium tuberculosis, holo-ACP (the product of EC 2.7.8.7, holo-[acyl-carrier-protein] synthase) is the preferred substrate [5].
Links to other databases: BRENDA, ERGO, EXPASY, GTD, KEGG, PDB, CAS registry number: 37257-17-3
References:
1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase. Methods Enzymol. 14 (1969) 50-53.
2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269-311. [PMID: 4561013]
3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases. J. Biol. Chem. 241 (1966) 2326-2332. [PMID: 5330116]
4. Joshi, V.C. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XXVI. Purification and properties of malonyl-coenzyme A--acyl carrier protein transacylase of Escherichia coli. Arch. Biochem. Biophys. 143 (1971) 493-505. [PMID: 4934182]
5. Kremer, L., Nampoothiri, K.M., Lesjean, S., Dover, L.G., Graham, S., Betts, J., Brennan, P.J., Minnikin, D.E., Locht, C. and Besra, G.S. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J. Biol. Chem. 276 (2001) 27967-27974. [PMID: 11373295]
6. Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J., O'Connell, J.D., 3rd, Khosla, C. and Stroud, R.M. Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11 (2003) 147-154. [PMID: 12575934]
7. Szafranska, A.E., Hitchman, T.S., Cox, R.J., Crosby, J. and Simpson, T.J. Kinetic and mechanistic analysis of the malonyl CoA:ACP transacylase from Streptomyces coelicolor indicates a single catalytically competent serine nucleophile at the active site. Biochemistry 41 (2002) 1421-1427. [PMID: 11814333]
Common name: β-ketoacyl-acyl-carrier-protein synthase I
Reaction: acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein] = 3-oxoacyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein]
Other name(s): β-ketoacyl-ACP synthase I; β-ketoacyl synthetase; β-ketoacyl-ACP synthetase; β-ketoacyl-acyl carrier protein synthetase; β-ketoacyl-[acyl carrier protein] synthase; β-ketoacylsynthase; condensing enzyme; 3-ketoacyl-acyl carrier protein synthase; fatty acid condensing enzyme; acyl-malonyl(acyl-carrier-protein)-condensing enzyme; acyl-malonyl acyl carrier protein-condensing enzyme; β-ketoacyl acyl carrier protein synthase; 3-oxoacyl-[acyl-carrier-protein] synthase; 3-oxoacyl:ACP synthase I; KASI; KAS I; FabF1; FabB
Systematic name: acyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating)
Comments: This enzyme is responsible for the chain-elongation step of dissociated (type II) fatty-acid biosynthesis. Escherichia coli mutants that lack this enzyme are deficient in unsaturated fatty acids. The enzyme can use fatty acyl thioesters of ACP (C2 to C16) as substrates, as well as fatty acyl thioesters of Co-A (C4 to C16) [4]. The substrate specificity is very similar to that of EC 2.3.1.179, β-ketoacyl-ACP synthase II, with the exception that the latter enzyme is far more active with palmitoleoyl-ACP (C16Δ9) as substrate, allowing the organism to regulate its fatty-acid composition with changes in temperature [4,5].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 9077-10-5
References:
1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase. Methods Enzymol. 14 (1969) 50-53.
2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269-311. [PMID: 4561013]
3. Toomey, R.E. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVI. Preparation and general properties of acyl-malonyl acyl carrier protein-condensing enzyme from Escherichia coli. J. Biol. Chem. 241 (1966) 1159-1165. [PMID: 5327099]
4. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250 (1975) 5289-5294. [PMID: 237914]
5. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β-ketoacyl-acyl carrier protein synthases I and II of Escherichia coli. J. Biol. Chem. 255 (1980) 11949-11956. [PMID: 7002930]
6. Wang, H. and Cronan, J.E. Functional replacement of the FabA and FabB proteins of Escherichia coli fatty acid synthesis by Enterococcus faecalis FabZ and FabF homologues. J. Biol. Chem. 279 (2004) 34489-34495. [PMID: 15194690]
7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612-636.
Common name: arginine N-succinyltransferase
Reaction: succinyl-CoA + L-arginine = CoA + N2-succinyl-L-arginine
For diagram, click here
Other name(s): arginine succinyltransferase; AstA; arginine and ornithine N2-succinyltransferase; AOST; AST
Systematic name: succinyl-CoA:L-arginine N2-succinyltransferase
Comments: Also acts on L-ornithine. This is the first enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.81 (succinylornithine transaminase), EC 1.2.1.71 (succinylglutamate-semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase) [2,6].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 99676-48-9
References:
1. Vander Wauven, C., Jann, A., Haas, D., Leisinger, T. and Stalon, V. N2-succinylornithine in ornithine catabolism of Pseudomonas aeruginosa. Arch. Microbiol. 150 (1988) 400-404. [PMID: 3144259]
2. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882-886. [PMID: 2865249]
3. Tricot, C., Vander Wauven, C., Wattiez, R., Falmagne, P. and Stalon, V. Purification and properties of a succinyltransferase from Pseudomonas aeruginosa specific for both arginine and ornithine. Eur. J. Biochem. 224 (1994) 853-861. [PMID: 7523119]
4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280-7290. [PMID: 9393691]
5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278-4286. [PMID: 9696779]
6. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314-352. [PMID: 3534538]
Common name: biphenyl synthase
Reaction: 3 malonyl-CoA + benzoyl-CoA = 4 CoA + 3,5-dihydroxybiphenyl + 4 CO2
Other name(s): BIS
Systematic name: malonyl-CoA:benzoyl-CoA malonyltransferase
Comments: A polyketide synthase that is involved in the production of the phytoalexin aucuparin. 2-Hydroxybenzoyl-CoA can also act as substrate but it leads to the derailment product 2-hydroxybenzoyltriacetic acid lactone. This enzyme uses the same starter substrate as EC 2.3.1.151, benzophenone synthase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Liu, B., Beuerle, T., Klundt, T. and Beerhues, L. Biphenyl synthase from yeast-extract-treated cell cultures of Sorbus aucuparia. Planta 218 (2004) 492-496. [PMID: 14595561]
Common name: diaminobutyrate acetyltransferase
Reaction: acetyl-CoA + L-2,4-diaminobutanoate = CoA + N4-acetyl-L-2,4-diaminobutanoate
For diagram, click here
Other name(s): L-2,4-diaminobutyrate acetyltransferase; L-2,4-diaminobutanoate acetyltransferase; EctA; diaminobutyric acid acetyltransferase; DABA acetyltransferase; 2,4-diaminobutanoate acetyltransferase; DAB acetyltransferase; DABAcT
Systematic name: acetyl-CoA:L-2,4-diaminobutanoate N4-acetyltransferase
Comments: Requires Na+ or K+ for maximal activity [3]. Ornithine, lysine, aspartate, and α-, β- and γ-aminobutanoate cannot act as substrates [3]. However, acetyl-CoA can be replaced by propanoyl-CoA, although the reaction proceeds more slowly [3]. Forms part of the ectoine-biosynthesis pathway, the other enzymes involved being EC 2.6.1.76, diaminobutyrate—2-oxoglutarate transaminase and EC 4.2.1.108, ectoine synthase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine. FEMS Microbiol. Lett. 71 (1990) 157-162.
2. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano, M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. J. Bacteriol. 181 (1999) 91-99. [PMID: 9864317]
3. Reshetnikov, A.S., Mustakhimov, I.I., Khmelenina, V.N. and Trotsenko, Y.A. Cloning, purification, and characterization of diaminobutyrate acetyltransferase from the halotolerant methanotroph Methylomicrobium alcaliphilum 20Z. Biochemistry (Mosc.) 70 (2005) 878-883. [PMID: 16212543]
4. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl. Environ. Microbiol. 68 (2002) 772-783. [PMID: 11823218]
5. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. Microbiology 143 (1997) 1141-1149. [PMID: 9141677]
Common name: β-ketoacyl-acyl-carrier-protein synthase II
Reaction: palmitoleoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = cis-vaccenoyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein]
Other name(s): KASII; KAS II; FabF; 3-oxoacyl-acyl carrier protein synthase I; β-ketoacyl-ACP synthase II
Systematic name: palmitoleoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating)
Comments: Involved in the dissociated (or type II) fatty acid biosynthesis system that occurs in plants and bacteria. While the substrate specificity of this enzyme is very similar to that of EC 2.3.1.41, β-ketoacyl-ACP synthase I, it differs in that palmitoleoyl-ACP is not a good substrate of EC 2.3.1.41 but is an excellent substrate of this enzyme [1,2]. The fatty-acid composition of Escherichia coli changes as a function of growth temperature, with the proportion of unsaturated fatty acids increasing with lower growth temperature. This enzyme controls the temperature-dependent regulation of fatty-acid composition, with mutants lacking this acivity being deficient in the elongation of palmitoleate to cis-vaccenate at low temperatures [3,4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250 (1975) 5289-5294. [PMID: 237914]
2. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β-ketoacyl-acyl carrier protein synthases I and II of Escherichia coli. J. Biol. Chem. 255 (1980) 11949-11956. [PMID: 7002930]
3. Price, A.C., Rock, C.O. and White, S.W. The 1.3-Angstrom-resolution crystal structure of β-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae. J. Bacteriol. 185 (2003) 4136-4143. [PMID: 12837788]
4. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr. β-Ketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis. J. Biol. Chem. 255 (1980) 3263-3265. [PMID: 6988423]
5. Magnuson, K., Carey, M.R. and Cronan, J.E., Jr. The putative fabJ gene of Escherichia coli fatty acid synthesis is the fabF gene. J. Bacteriol. 177 (1995) 3593-3595. [PMID: 7768872]
6. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612-636.
Common name: β-ketoacyl-acyl-carrier-protein synthase III
Reaction: acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO2
Other name(s): 3-oxoacyl:ACP synthase III; 3-ketoacyl-acyl carrier protein synthase III; KASIII; KAS III; FabH; β-ketoacyl-acyl carrier protein synthase III; β-ketoacyl-ACP synthase III; β-ketoacyl (acyl carrier protein) synthase III
Systematic name: acetyl-CoA:malonyl-[acyl-carrier-protein] C-acyltransferase
Comments: Involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and bacteria. In contrast to EC 2.3.1.41 (β-ketoacyl-ACP synthase I) and EC 2.3.1.179 (β-ketoacyl-ACP synthase II), this enzyme specifically uses CoA thioesters rather than acyl-ACP as the primer [1]. In addition to the above reaction, the enzyme can also catalyse the reaction of EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, but to a much lesser extent [1]. The enzyme is responsible for initiating both straight- and branched-chain fatty-acid biosynthesis [2], with the substrate specificity in an organism reflecting the fatty-acid composition found in that organism [2,5]. For example, Streptococcus pneumoniae, a Gram-positive bacterium, is able to use both straight- and branched-chain (C4—C6) acyl-CoA primers [3] whereas Escherichia coli, a Gram-negative organism, uses primarily short straight-chain acyl CoAs, with a preference for acetyl-CoA [4,5].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of the β-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem. 267 (1992) 6807-6814. [PMID: 1551888]
2. Han, L., Lobo, S. and Reynolds, K.A. Characterization of β-ketoacyl-acyl carrier protein synthase III from Streptomyces glaucescens and its role in initiation of fatty acid biosynthesis. J. Bacteriol. 180 (1998) 4481-4486. [PMID: 9721286]
3. Khandekar, S.S., Gentry, D.R., Van Aller, G.S., Warren, P., Xiang, H., Silverman, C., Doyle, M.L., Chambers, P.A., Konstantinidis, A.K., Brandt, M., Daines, R.A. and Lonsdale, J.T. Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae β-ketoacyl-acyl carrier protein synthase III (FabH). J. Biol. Chem. 276 (2001) 30024-30030. [PMID: 11375394]
4. Choi, K.H., Kremer, L., Besra, G.S. and Rock, C.O. Identification and substrate specificity of β-ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem. 275 (2000) 28201-28207. [PMID: 10840036]
5. Qiu, X., Choudhry, A.E., Janson, C.A., Grooms, M., Daines, R.A., Lonsdale, J.T. and Khandekar, S.S. Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus. Protein Sci. 14 (2005) 2087-2094. [PMID: 15987898]
6. Li, Y., Florova, G. and Reynolds, K.A. Alteration of the fatty acid profile of Streptomyces coelicolor by replacement of the initiation enzyme 3-ketoacyl acyl carrier protein synthase III (FabH). J. Bacteriol. 187 (2005) 3795-3799. [PMID: 15901703]
7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612-636.
Common name: lipoyl(octanoyl) transferase
Reaction: octanoyl-[acyl carrier protein] + protein = protein N6-(octanoyl)lysine + acyl carrier protein
Glossary: lipoyl group
Other name(s): LipB; lipoyl (octanoyl)-[acyl-carrier-protein]-protein N-lipoyltransferase; lipoyl (octanoyl)-acyl carrier protein:protein transferase; lipoate/octanoate transferase; lipoyltransferase; octanoyl-[acyl carrier protein]-protein N-octanoyltransferase; lipoyl(octanoyl)transferase
Systematic name: octanoyl-[acyl carrier protein]:protein N-octanoyltransferase
Comments: This is the first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,3]. Lipoyl-ACP can also act as a substrate [4]. The remaining steps in the production of lipoyl cofactor involve EC 2.8.1.8, lipoyl synthase and EC 2.7.7.63, lipoate—protein ligase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269-282. [PMID: 15642479]
2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411-6420. [PMID: 1655709]
3. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903-17906. [PMID: 9218413]
4. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293-1302. [PMID: 14700636]
5. Wada, M., Yasuno, R., Jordan, S.W., Cronan, J.E., Jr. and Wada, H. Lipoic acid metabolism in Arabidopsis thaliana: cloning and characterization of a cDNA encoding lipoyltransferase. Plant Cell Physiol. 42 (2001) 650-656. [PMID: 11427685]
Common name: N-hydroxythioamide S-β-glucosyltransferase
Reaction: UDP-glucose + N-hydroxy-2-phenylethanethioamide = UDP + desulfoglucotropeolin
For diagram, click here
Other name(s): desulfoglucosinolate-uridine diphosphate glucosyltransferase; uridine diphosphoglucose-thiohydroximate glucosyltransferase; thiohydroximate β-D-glucosyltransferase; UDPG:thiohydroximate glucosyltransferase; thiohydroximate S-glucosyltransferase; thiohydroximate glucosyltransferase; UDP-glucose:thiohydroximate S-β-D-glucosyltransferase
Systematic name: UDP-glucose:N-hydroxy-2-phenylethanethioamide S-β-D-glucosyltransferase
Comments: Involved with EC 2.8.2.24, desulfoglucosinolate sulfotransferase, in the biosynthesis of thioglucosides in cruciferous plants.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9068-14-8
References:
1. Jain, J.C., Reed, D.W., Groot Wassink, J.W.D. and Underhill, E.W. A radioassay of enzymes catalyzing the glucosylation and sulfation steps of glucosinolate biosynthesis in Brassica species. Anal. Biochem. 178 (1989) 137-140. [PMID: 2524977]
2. Reed, D.W., Davin, L., Jain, J.C., Deluca, V., Nelson, L. and Underhill, E.W. Purification and properties of UDP-glucose:thiohydroximate glucosyltransferase from Brassica napus L. seedlings. Arch. Biochem. Biophys. 305 (1993) 526-532. [PMID: 8373190]
3. Fahey, J.W., Zalcmann, A.T. and Talalay, P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56 (2001) 5-51. [PMID: 11198818]
4. Grubb, C.D., Zipp, B.J., Ludwig-Müller, J., Masuno, M.N., Molinski, T.F. and Abel, S. Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis and auxin homeostasis. Plant J. 40 (2004) 893-908.
Common name: 6G-fructosyltransferase
Reaction: [1-β-D-fructofuranosyl-(2→1)-]m+1 α-D-glucopyranoside + [1-β-D-fructofuranosyl-(2→1)-]n+1 α-D-glucopyranoside = [1-β-D-fructofuranosyl-(2→1)-]m α-D-glucopyranoside + [1-β-D-fructofuranosyl-(2→1)-]n+1 β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside (m > 0; n ≥ 0)
Other name(s): fructan:fructan 6G-fructosyltransferase; 1F(1-β-D-fructofuranosyl)m sucrose:1F(1-β-D-fructofuranosyl)nsucrose 6G-fructosyltransferase; 6G-FFT; 6G-FT; 6G-fructotransferase
Systematic name: 1F-oligo[β-D-fructofuranosyl-(2→1)-]sucrose 6G-β-D-fructotransferase
Comments: This enzyme catalyses the transfer of the terminal (2→1)-linked β-D-fructosyl group of a mono- or oligosaccharide substituent on O-1 of the fructose residue of sucrose onto O-6 of its glucose residue [1]. For example, if 1-kestose [1F-(β-D-fructofuranosyl)sucrose] is both the donor and recipient in the reaction shown above, i.e., if m = 1 and n = 1, then the products will be sucrose and 1F,6G-di-β-D-fructofuranosylsucrose. In this notation, the superscripts F and G are used to specify whether the fructose or glucose residue of the sucrose carries the substituent. Alternatively, this may be indicated by the presence and/or absence of primes (see 2-Carb-36.2). Sucrose cannot be a donor substrate in the reaction (i.e. m cannot be zero) and inulin cannot act as an acceptor. Side reactions catalysed are transfer of a β-D-fructosyl group between compounds of the structure 1F-(1-β-D-fructofuranosyl)m-6G-(1-β-D-fructofuranosyl)n sucrose, where m ≥ 0 and n = 1 for the donor, and m ≥ 0 and n ≥ 0 for the acceptor.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Shiomi, N. Purification and characterisation of 6G-fructosyltransferase from the roots of asparagus (Asparagus officinalis L.). Carbohydr. Res. 96 (1981) 281-292.
2. Shiomi, N. Reverse reaction of fructosyl transfer catalysed by asparagus 6G-fructosyltransferase. Carbohydr. Res. 106 (1982) 166-169.
3. Shiomi, N. and Ueno, K. Cloning and expression of genes encoding fructosyltransferases from higher plants in food technology. J. Appl. Glycosci. 51 (2004) 177-183.
4. Ueno, K., Onodera, S., Kawakami, A., Yoshida, M. and Shiomi, N. Molecular characterization and expression of a cDNA encoding fructan:fructan 6G-fructosyltransferase from asparagus (Asparagus officinalis). New Phytol. 165 (2005) 813-824. [PMID: 15720693]
Common name: N-acetyl-β-glucosaminyl-glycoprotein 4-β-N-acetylgalactosaminyltransferase
Reaction: UDP-N-acetyl-D-galactosamine + N-acetyl-β-D-glucosaminyl group = UDP + N-acetyl-β-D-galactosaminyl-(1→4)-N-acetyl-β-D-glucosaminyl group
Glossary: N,N'-diacetyllactosediamine = N-acetyl-β-D-galactosaminyl-(1→4)-N-acetyl-D-glucosamine
Other name(s): β1,4-N-acetylgalactosaminyltransferase III; β4GalNAc-T3; β1,4-N-acetylgalactosaminyltransferase IV; β4GalNAc-T4
Systematic name: UDP-N-acetyl-D-galactosamine:N-acetyl-D-glucosaminyl-group β-1,4-N-acetylgalactosaminyltransferase
Comments: The enzyme from human can transfer N-acetyl-D-galactosamine (GalNAc) to N-glycan and O-glycan substrates that have N-acetyl-D-glucosamine (GlcNAc) but not D-glucuronic acid (GlcUA) at their non-reducing end. The N-acetyl-β-D-glucosaminyl group is normally on a core oligosaccharide although benzyl glycosides have been used in enzyme-characterization experiments. Some glycohormones, e.g. lutropin and thyrotropin contain the N-glycan structure containing the N-acetyl-β-D-galactosaminyl-(1→4)-N-acetyl-β-D-glucosaminyl group.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Sato, T., Gotoh, M., Kiyohara, K., Kameyama, A., Kubota, T., Kikuchi, N., Ishizuka, Y., Iwasaki, H., Togayachi, A., Kudo, T., Ohkura, T., Nakanishi, H. and Narimatsu, H. Molecular cloning and characterization of a novel human β1,4-N-acetylgalactosaminyltransferase, β4GalNAc-T3, responsible for the synthesis of N,N'-diacetyllactosediamine, GalNAc β1-4GlcNAc. J. Biol. Chem. 278 (2003) 47534-47544. [PMID: 12966086]
2. Gotoh, M., Sato, T., Kiyohara, K., Kameyama, A., Kikuchi, N., Kwon, Y.D., Ishizuka, Y., Iwai, T., Nakanishi, H. and Narimatsu, H. Molecular cloning and characterization of β1,4-N-acetylgalactosaminyltransferases IV synthesizing N,N'-diacetyllactosediamine. FEBS Lett. 562 (2004) 134-140. [PMID: 15044014]
Common name: phosphoserine transaminase
Reaction: (1) O-phospho-L-serine + 2-oxoglutarate = 3-phosphonooxypyruvate + L-glutamate
(2) 4-phosphonooxy-L-threonine + 2-oxoglutarate = (3R)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + L-glutamate
For diagram, click here or here for mechanism click here.
Other name(s): PSAT; phosphoserine aminotransferase; 3-phosphoserine aminotransferase; hydroxypyruvic phosphate-glutamic transaminase; L-phosphoserine aminotransferase; phosphohydroxypyruvate transaminase; phosphohydroxypyruvic-glutamic transaminase; phosphoserine aminotransferase; 3-O-phospho-L-serine:2-oxoglutarate aminotransferase; SerC; PdxC; 3PHP transaminase
Systematic name: O-phospho-L-serine:2-oxoglutarate aminotransferase
Comments: A pyridoxal-phosphate protein. This enzyme catalyses the second step in the phosphorylated pathway of serine biosynthesis in Escherichia coli [2,3]. It also catalyses the third step in the biosynthesis of the coenzyme pyridoxal 5'-phosphate in Escherichia coli (using Reaction 2 above) [3]. In Escherichia coli, pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5'-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5'-phosphate as substrate). Pyridoxal phosphate is the cofactor for both activities and therefore seems to be involved in its own biosynthesis [4]. Non-phosphorylated forms of serine and threonine are not substrates [4].
Links to other databases: BRENDA, ERGO, EXPASY, GTD, KEGG, PDB, CAS registry number: 9030-90-4
References:
1. Hirsch, H. and Greenberg, D.M. Studies on phosphoserine aminotransferase of sheep brain. J. Biol. Chem. 242 (1967) 2283-2287. [PMID: 6022873]
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. Drewke, C., Klein, M., Clade, D., Arenz, A., Müller, R. and Leistner, E. 4-O-phosphoryl-L-threonine, a substrate of the pdxC(serC) gene product involved in vitamin B6 biosynthesis. FEBS Lett. 390 (1996) 179-182. [PMID: 8706854]
5. Zhao, G. and Winkler, M.E. 4-Phospho-hydroxy-L-threonine is an obligatory intermediate in pyridoxal 5'-phosphate coenzyme biosynthesis in Escherichia coli K-12. FEMS Microbiol. Lett. 135 (1996) 275-280. [PMID: 8595869]
Common name: diaminobutyrate—2-oxoglutarate transaminase
Reaction: L-2,4-diaminobutanoate + 2-oxoglutarate = L-aspartate 4-semialdehyde + L-glutamate
For diagram, click here
Other name(s): L-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase; 2,4-diaminobutyrate 4-aminotransferase; diaminobutyrate aminotransferase; DABA aminotransferase; DAB aminotransferase; EctB; diaminibutyric acid aminotransferase; L-2,4-diaminobutyrate:2-oxoglutarate 4-aminotransferase
Systematic name: L-2,4-diaminobutanoate:2-oxoglutarate 4-aminotransferase
Comments: A pyridoxal-phosphate protein that requires potassium for activity [4]. In the proteobacterium Acinetobacter baumannii, this enzyme is a product of the ddc gene that also encodes EC 4.1.1.85, diaminobutyrate decarboxylase. Differs from EC 2.6.1.46, diaminobutyrate—pyruvate transaminase, which has pyruvate as the amino-group acceptor. This is the first enzyme in the ectoine-biosynthesis pathway, the other enzymes involved being EC 2.3.1.178, diaminobutyrate acetyltransferase and EC 4.2.1.108, ectoine synthase [3,4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 196622-96-5
References:
1. Ikai, H. and Yamamoto, S. Identification and analysis of a gene encoding L-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production pathway in Acinetobacter baumannii. J. Bacteriol. 179 (1997) 5118-5125. [PMID: 9260954]
2. Ikai, H. and Yamamoto, S. Two genes involved in the 1,3-diaminopropane production pathway in Haemophilus influenzae. Biol. Pharm. Bull. 21 (1998) 170-173. [PMID: 9514614]
3. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine. FEMS Microbiol. Lett. 71 (1990) 157-162.
4. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano, M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. J. Bacteriol. 181 (1999) 91-99. [PMID: 9864317]
5. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl. Environ. Microbiol. 68 (2002) 772-783. [PMID: 11823218]
6. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. Microbiology 143 (1997) 1141-1149. [PMID: 9141677]
Common name: succinylornithine transaminase
Reaction: N2-succinyl-L-ornithine + 2-oxoglutarate = N-succinyl-L-glutamate 5-semialdehyde + L-glutamate
For diagram, click here
Other name(s): succinylornithine aminotransferase; N2-succinylornithine 5-aminotransferase; AstC; SOAT
Systematic name: N2-succinyl-L-ornithine:2-oxoglutarate 5-aminotransferase
Comments: A pyridoxal-phosphate protein. Also acts on N2-acetyl-L-ornithine and L-ornithine, but more slowly [3]. In Pseudomonas aeruginosa, the arginine-inducible succinylornithine transaminase, acetylornithine transaminase (EC 2.6.1.11) and ornithine aminotransferase (EC 2.6.1.13) activities are catalysed by the same enzyme, but this is not the case in all species [5]. This is the third enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.81 (succinylornithine transaminase), EC 1.2.1.71 (succinylglutamate-semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase) [3, 6]. Of the five enzymes involved in arginine catabolism, this is the only one that is also involved in ornithine catabolism [4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882-886. [PMID: 2865249]
2. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278-4286. [PMID: 9696779]
3. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314-352. [PMID: 3534538]
4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280-7290. [PMID: 9393691]
5. Stalon, V., Vander Wauven, C., Momin, P. and Legrain, C. Catabolism of arginine, citrulline and ornithine by Pseudomonas and related bacteria. J. Gen. Microbiol. 133 (1987) 2487-2495. [PMID: 3129535]
Common name: pyridoxine 5'-phosphate synthase
Reaction: 1-deoxy-D-xylulose 5-phosphate + 3-amino-2-oxopropyl phosphate = pyridoxine 5'-phosphate + phosphate + 2 H2O
For diagram, click here
Other name(s): pyridoxine 5-phosphate phospho lyase; PNP synthase; PdxJ
Systematic name: 1-deoxy-D-xylulose-5-phosphate:3-amino-2-oxopropyl phosphate 3-amino-2-oxopropyltransferase (phosphate-hydrolysing; cyclizing)
Comments: In Escherichia coli, the coenzyme pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5'-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5'-phosphate as substrate). 1-Deoxy-D-xylulose cannot replace 1-deoxy-D-xylulose 5-phosphate as a substrate [3].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Garrido-Franco, M. Pyridoxine 5'-phosphate synthase: de novo synthesis of vitamin B6 and beyond. Biochim. Biophys. Acta 1647 (2003) 92-97. [PMID: 12686115]
2. Garrido-Franco, M., Laber, B., Huber, R. and Clausen, T. Enzyme-ligand complexes of pyridoxine 5'-phosphate synthase: implications for substrate binding and catalysis. J. Mol. Biol. 321 (2002) 601-612. [PMID: 12206776]
3. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B6 biosynthesis: formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein. FEBS Lett. 449 (1999) 45-48. [PMID: 10225425]
4. Franco, M.G., Laber, B., Huber, R. and Clausen, T. Structural basis for the function of pyridoxine 5'-phosphate synthase. Structure 9 (2001) 245-253. [PMID: 11286891]
Common name: inositol-polyphosphate multikinase
Reaction: (1) ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
(2) ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate = ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
For diagram, click here
Other name(s): IpK2; IP3/IP4 6-/3-kinase; IP3/IP4 dual-specificity 6-/3-kinase; IpmK; ArgRIII; AtIpk2α; AtIpk2β; inositol polyphosphate 6-/3-/5-kinase
Systematic name: ATP:1D-myo-inositol-1,4,5-trisphosphate 6-phosphotransferase
Comments: This enzyme also phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4, Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5, and Ins(1,3,4,5,6)P4 to Ins(PP)P4, isomer unknown. The enzyme from the plant Arabidopsis thaliana can also phosphorylate Ins(1,3,4,6)P4 and Ins(1,2,3,4,6)P5 at the D-5-position to produce 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate (InsP6), respectively [3]. Yeast produce InsP6 from Ins(1,4,5)P3 by the actions of this enzyme and EC 2.7.1.158, inositol-pentakisphosphate 2-kinase [4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Saiardi, A., Erdjument-Bromage, H., Snowman, A.M., Tempst, P. and Snyder, S.H. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr. Biol. 9 (1999) 1323-1326. [PMID: 10574768]
2. Odom, A.R., Stahlberg, A., Wente, S.R. and York, J.D. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 287 (2000) 2026-2029. [PMID: 10720331]
3. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J. Biol. Chem. 277 (2002) 42711-42718. [PMID: 12226109]
4. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the production of inositol hexakisphosphate in human cells. J. Biol. Chem. 280 (2005) 1911-1920. [PMID: 15531582]
Common name: inositol-pentakisphosphate 2-kinase
Reaction: ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol hexakisphosphate
Other name(s): IP5 2-kinase; Gsl1p; Ipk1p; Plc1p; inositol polyphosphate kinase; inositol 1,3,4,5,6-pentakisphosphate 2-kinase; Ins(1,3,4,5,6)P5 2-kinase
Systematic name: ATP:1D-myo-inositol 1,3,4,5,6-pentakisphosphate 2-phosphotransferase
Comments: The enzyme can also use Ins(1,4,5,6)P4 [2] and Ins(1,4,5)P3 [3] as substrate. Inositol hexakisphosphate (phytate) accumulates in storage protein bodies during seed development and, when hydrolysed, releases stored nutrients to the developing seedling before the plant is capable of absorbing nutrients from its environment [5].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. York, J.D., Odom, A.R., Murphy, R., Ives, E.B. and Wente, S.R. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 285 (1999) 96-100. [PMID: 10390371]
2. Phillippy, B.Q., Ullah, A.H. and Ehrlich, K.C. Purification and some properties of inositol 1,3,4,5,6-Pentakisphosphate 2-kinase from immature soybean seeds. J. Biol. Chem. 269 (1994) 28393-28399. [PMID: 7961779]
3. Ongusaha, P.P., Hughes, P.J., Davey, J. and Michell, R.H. Inositol hexakisphosphate in Schizosaccharomyces pombe: synthesis from Ins(1,4,5)P3 and osmotic regulation. Biochem. J. 335 (1998) 671-679. [PMID: 9794810]
4. Miller, A.L., Suntharalingam, M., Johnson, S.L., Audhya, A., Emr, S.D. and Wente, S.R. Cytoplasmic inositol hexakisphosphate production is sufficient for mediating the Gle1-mRNA export pathway. J. Biol. Chem. 279 (2004) 51022-51032. [PMID: 15459192]
5. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J. Biol. Chem. 277 (2002) 42711-42718. [PMID: 12226109]
Common name: inositol-1,3,4-trisphosphate 5/6-kinase
Reaction: (1) ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
(2) ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate
Other name(s): Ins(1,3,4)P3 5/6-kinase; inositol trisphosphate 5/6-kinase
Systematic name: ATP:1D-myo-inositol 1,3,4-trisphosphate 5-phosphotransferase
Comments: In humans, this enzyme, along with EC 2.7.1.127 (inositol-trisphosphate 3-kinase), EC 2.7.1.140 (inositol-tetrakisphosphate 5-kinase) and EC 2.7.1.158 (inositol pentakisphosphate 2-kinase) is involved in the production of inositol hexakisphosphate (InsP6). InsP6 is involved in many cellular processes, including mRNA export from the nucleus [2]. Yeast do not have this enzyme, so produce InsP6 from Ins(1,4,5)P3 by the actions of EC 2.7.1.151 (inositol-polyphosphate multikinase) and EC 2.7.1.158 (inositol-pentakisphosphate 2-kinase) [2].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Wilson, M.P. and Majerus, P.W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme. J. Biol. Chem. 271 (1996) 11904-11910. [PMID: 8662638]
2. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the production of inositol hexakisphosphate in human cells. J. Biol. Chem. 280 (2005) 1911-1920. [PMID: 15531582]
Common name: UMP kinase
Reaction: ATP + UMP = ADP + UDP
Other name(s): uridylate kinase; UMPK; uridine monophosphate kinase; PyrH; UMP-kinase; SmbA
Systematic name: ATP:UMP phosphotransferase
Comments: This enzyme is strictly specific for UMP as substrate and is used by prokaryotes in the de novo synthesis of pyrimidines, in contrast to eukaryotes, which use the dual-specificity enzyme UMP/CMP kinase (EC 2.7.4.14) for the same purpose [2]. This enzyme is the subject of feedback regulation, being inhibited by UTP and activated by GTP [1].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Serina, L., Blondin, C., Krin, E., Sismeiro, O., Danchin, A., Sakamoto, H., Gilles, A.M. and BÌ¢rzu O. Escherichia coli UMP-kinase, a member of the aspartokinase family, is a hexamer regulated by guanine nucleotides and UTP. Biochemistry 34 (1995) 5066-5074. [PMID: 7711027]
2. Marco-Marin, C., Gil-Ortiz, F. and Rubio, V. The crystal structure of Pyrococcus furiosus UMP kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide biosynthesis. J. Mol. Biol. 352 (2005) 438-454. [PMID: 16095620]
Common name: lipoate—protein ligase
Reaction: (1) ATP + lipoate = diphosphate + lipoyl-AMP
(2) lipoyl-AMP + protein = protein N6-(lipoyl)lysine + AMP
Other name(s): LplA; lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B
Systematic name: ATP:lipoate adenylyltransferase
Comments: Requires Mg2+. Selenolipoate and 6-thio-octanoate can also act as substrates, but more slowly [2]. Both D- and L-lipoate can act as a substrate but there is a preference for the naturally occurring D-form. The lipoyl cofactor is essential for the function of several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [6]. This enzyme attaches lipoic acid to the lipoyl domains of these proteins. The remaining steps in the production of lipoyl cofactor involve EC 2.3.1.181, lipoyl(octanoyl) transferase and EC 2.8.1.8, lipoyl synthase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Morris, T.W., Reed, K.E. and Cronan, J.E., Jr. Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. J. Biol. Chem. 269 (1994) 16091-16100. [PMID: 8206909]
2. Green, D.E., Morris, T.W., Green, J., Cronan, J.E., Jr. and Guest, J.R. Purification and properties of the lipoate protein ligase of Escherichia coli. Biochem. J. 309 (1995) 853-862. [PMID: 7639702]
3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293-1302. [PMID: 14700636]
4. Kim do, J., Kim, K.H., Lee, H.H., Lee, S.J., Ha, J.Y., Yoon, H.J. and Suh, S.W. Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains. J. Biol. Chem. 280 (2005) 38081-38089. [PMID: 16141198]
5. Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A. and Taniguchi, H. Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site. J. Biol. Chem. 280 (2005) 33645-33651. [PMID: 16043486]
6. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903-17906. [PMID: 9218413]
Common name: biotin synthase
Reaction: dethiobiotin + sulfur + 2 S-adenosyl-L-methionine = biotin + 2 L-methionine + 2 5'-deoxyadenosyl radicals
Systematic name: dethiobiotin:sulfur sulfurtransferase
Comments: This single-turnover enzyme is a member of the 'radical SAM' (S-adenosylmethionine; AdoMet) family, all members of which contain the motif CX3CX2C. The enzyme contains a [2Fe-2S] and a [4Fe-4S] centre. The [4Fe-4S]2+,+ complex mediates the electron transfer required for the reductive cleavage of AdoMet into methionine and a deoxyadenosyl radical. Two molecules of AdoMet are consumed to activate positions 6 and 9 of dethiobiotin. This is required to abstract a hydrogen atom, which is then replaced by the sulfur atom at postition C-6. Sulfur insertion into dethiobiotin takes place with retention of configuration [3]. The sulfur donor has not been identified to date - it is neither elemental sulfur nor from SAM, but it has been postulated that it may be from the [2Fe-2S] centre [4].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 80146-93-6 (204794-88-7, 179608-56-1, 209603-31-6, 153554-27-9, 174764-24-0 and 215108-34-2)
References:
1. Shiuan, D. and Campbell, A. Transcriptional regulation and gene arrangement of Escherichia coli, Citrobacter freundii and Salmonella typhimurium biotin operons. Gene 67 (1988) 203-211. [PMID: 2971595]
2. Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A. and Flint, D.H. The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase. Arch. Biochem. Biophys. 309 (1994) 29-35. [PMID: 8117110]
3. Trainor, D.A., Parry, R.J. and Gitterman, A. Biotin biosynthesis. 2. Stereochemistry of sulfur introduction at C-4 of dethiobiotin. J. Am. Chem. Soc. 102 (1980) 1467-1468.
4. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A. Biotin synthase mechanism: an overview. Biochem. Soc. Trans. 33 (2005) 820-823. [PMID: 16042606]
5. Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T. and Drennan, C.L. Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical enzyme. Science 303 (2004) 76-79. [PMID: 14704425]
6. Ugulava, N.B., Gibney, B.R. and Jarrett, J.T. Biotin synthase contains two distinct iron-sulfur cluster binding sites: chemical and spectroelectrochemical analysis of iron-sulfur cluster interconversions. Biochemistry 40 (2001) 8343-8351. [PMID: 11444981]
Common name: lipoyl synthase
Reaction: protein N6-(octanoyl)lysine + 2 sulfur + 2 S-adenosyl-L-methionine = protein N6-(lipoyl)lysine + 2 L-methionine + 2 5'-deoxyadenosyl radicals
Other name(s): LS; LipA
Systematic name: protein N6-(octanoyl)lysine:sulfur sulfurtransferase
Comments: This enzyme is a member of the 'radical SAM' (S-adenosylmethionine; AdoMet) family, all members of which contain the motif CX3CX2C. Catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, which is the insertion of two sulfur atoms into an eight-carbon saturated fatty-acyl chain at C-6 and C-8. The lipoyl cofactor is essential for the function of several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,5]. The reaction starts by using an electron from the reduced form of the enzyme's [4Fe-4S] cluster to split AdoMet into methionine and a 5'-deoxyadenosyl radical. The high-energy 5'-deoxyadenosyl radical then initiates catalysis by abstracting a key hydrogen atom from the relevant substrate [1]. The sulfur atoms are inserted with inversion of configuration [4]. The other enzymes involved in the biosynthesis of lipoyl cofactor are EC 2.3.1.181, lipoyl(octanoyl) transferase and EC 2.7.7.63, lipoate—protein ligase.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Cicchillo, R.M. and Booker, S.J. Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide. J. Am. Chem. Soc. 127 (2005) 2860-2861. [PMID: 15740115]
2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411-6420. [PMID: 1655709]
3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293-1302. [PMID: 14700636]
4. Cicchillo, R.M., Iwig, D.F., Jones, A.D., Nesbitt, N.M., Baleanu-Gogonea, C., Souder, M.G., Tu, L. and Booker, S.J. Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid. Biochemistry 43 (2004) 6378-6386. [PMID: 15157071]
5. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903-17906. [PMID: 9218413]
6. Miller, J.R., Busby, R.W., Jordan, S.W., Cheek, J., Henshaw, T.F., Ashley, G.W., Broderick, J.B., Cronan, J.E., Jr. and Marletta, M.A. Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein. Biochemistry 39 (2000) 15166-15178. [PMID: 11106496]