Continued from EC 6.2.1
EC 6.3.1 Acid—Ammonia (or Amine) Ligases (Amide Synthases)
EC 6.3.2 Acid—Amino-Acid Ligases (Peptide Synthases)
EC 6.3.3 Cyclo-Ligases
EC 6.3.4 Other Carbon—Nitrogen Ligases
EC 6.3.5 Carbon—Nitrogen Ligases with Glutamine as Amido-N-Donor
Accepted name: aspartate—ammonia ligase
Reaction: ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine
Other name(s): asparagine synthetase; L-asparagine synthetase
Systematic name: L-aspartate:ammonia ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-69-2
References:
1. Ravel, J.M., Norton, S.J., Humphreys, J.S. and Shive, W. Asparagine biosynthesis in Lactobacillus arabinosus and its control by asparagine through enzyme inhibition and repression. J. Biol. Chem. 237 (1962) 2845-2849.
2. Webster, G.C. and Varner, J.E. Aspartate metabolism and asparagine synthesis in plant systems. J. Biol. Chem. 215 (1955) 91-99.
Accepted name: glutamine synthetase
Reaction: ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
For diagram of reaction click here.
Other name(s): glutamate—ammonia ligase; glutamylhydroxamic synthetase; L-glutamine synthetase; GS
Systematic name: L-glutamate:ammonia ligase (ADP-forming)
Comments: Glutamine synthetase, which catalyses the incorporation of ammonium into glutamate, is a key enzyme of nitrogen metabolism found in all domains of life. Several types have been described, differing in their oligomeric structures and cofactor requirements.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9023-70-5
References:
1. Elliott, W.H. Isolation of glutamine synthetase and glutamotransferase from green peas. J. Biol. Chem. 201 (1953) 661-672. [PMID: 13061404]
2. Fry, B.A. Glutamine synthesis by Micrococcus pyogenes var. aureus. Biochem. J. 59 (1955) 579-589. [PMID: 14363150]
3. Lajtha, A., Mela, P. and Waelsch, H. Manganese-dependent glutamotransferase. J. Biol. Chem. 205 (1953) 553-564. [PMID: 13129232]
4. Meister, A. Glutamine synthesis. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 6, Academic Press, New York, 1962, pp. 443-468.
5. Woolfolk, C.A., Shapiro, B. and Stadtman, E.R. Regulation of glutamine synthetase. I. Purification and properties of glutamine synthetase from Escherichia coli. Arch. Biochem. Biophys. 116 (1966) 177-192. [PMID: 5336023]
6. Kumada, Y., Benson, D.R., Hillemann, D., Hosted, T.J., Rochefort, D.A., Thompson, C.J., Wohlleben, W. and Tateno, Y. Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes. Proc. Natl. Acad. Sci. USA 90 (1993) 3009-3013. [PMID: 8096645]
7. Llorca, O., Betti, M., Gonzalez, J.M., Valencia, A., Marquez, A.J. and Valpuesta, J.M. The three-dimensional structure of an eukaryotic glutamine synthetase: functional implications of its oligomeric structure. J. Struct. Biol. 156 (2006) 469-479. [PMID: 16884924]
8. Martinez-Espinosa, R.M., Esclapez, J., Bautista, V. and Bonete, M.J. An octameric prokaryotic glutamine synthetase from the haloarchaeon Haloferax mediterranei. FEMS Microbiol. Lett. 264 (2006) 110-116. [PMID: 17020556]
[EC 6.3.1.3 Transferred entry: now EC 6.3.4.13 phosphoribosylamine—glycine ligase (created 1961, deleted 1972)]
Accepted name: aspartate—ammonia ligase (ADP-forming)
Reaction: ATP + L-aspartate + NH3 = ADP + phosphate + L-asparagine
Other name(s): asparagine synthetase (ADP-forming); asparagine synthetase (adenosine diphosphate-forming)
Systematic name: L-aspartate:ammonia ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-61-9
References:
1. Nair, P.M. Asparagine synthetase from γ-irradiated potatoes. Arch. Biochem. Biophys. 133 (1969) 208-215. [PMID: 5820987]
Accepted name: NAD+ synthase
Reaction: ATP + deamido-NAD+ + NH3 = AMP + diphosphate + NAD+
Other name(s): NAD synthetase; NAD synthase; nicotinamide adenine dinucleotide synthetase; diphosphopyridine nucleotide synthetase
Systematic name: deamido-NAD+:ammonia ligase (AMP-forming)
Comments: L-Glutamine also acts, more slowly, as amido-donor [cf. EC 6.3.5.1, NAD+ synthase (glutamine-hydrolysing)].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-69-3
References:
1. Spencer, R.L. and Preiss, J. Biosynthesis of diphosphopyridine nucleotide. The purification and the properties of diphosphopyridine nucleotide synthetase from Escherichia coli B. J. Biol. Chem. 242 (1967) 385-392. [PMID: 4290215]
Accepted name: glutamate—ethylamine ligase
Reaction: ATP + L-glutamate + ethylamine = ADP + phosphate + N5-ethyl-L-glutamine
Other name(s): N5-ethyl-L-glutamine synthetase; theanine synthetase; N5-ethylglutamine synthetase
Systematic name: L-glutamate:ethylamine ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 62213-31-4
References:
1. Sasaoka, K. and Kito, M. Synthesis of theanine by tea seedling homogenate. Agric. Biol. Chem. 28 (1964) 313-317.
2. Sasaoka, K., Kito, M. and Inagaki, H. Studies on the biosynthesis of theanine in tea seedlings. Synthesis of theanine by the homogenate of tea seedlings. Agric. Biol. Chem. 27 (1963) 467-468.
3. Sasaoka, K., Kito, M. and Onishi, Y. Some properties of the theanine synthesizing enzyme in tea seedlings. Agric. Biol. Chem. 29 (1965) 984-988.
Accepted name: 4-methyleneglutamate—ammonia ligase
Reaction: ATP + 4-methylene-L-glutamate + NH3 = AMP + diphosphate + 4-methylene-L-glutamine
Other name(s): 4-methyleneglutamine synthetase
Systematic name: 4-methylene-L-glutamate:ammonia ligase (AMP-forming)
Comments: Glutamine can act instead of NH3, but more slowly.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 85537-85-5
References:
1. Winter, H.C., Su, T.-Z. and Dekker, E.E. 4-Methyleneglutamine synthetase: a new amide synthetase present in germinating peanuts. Biochem. Biophys. Res. Commun. 111 (1983) 484-489. [PMID: 6838571]
Accepted name: glutathionylspermidine synthase
Reaction: glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate
For diagram click here.
Glossary: glutathione = γ-L-glutamyl-L-cysteinyl-glycine
spermidine
Other name(s): glutathione:spermidine ligase (ADP-forming)
Systematic name: γ-L-Glutamyl-L-cysteinyl-glycine:spermidine ligase (ADP-forming) [spermidine is numbered so that atom N-1 is in the amino group of the aminopropyl part of the molecule]
Comments: Requires magnesium ions. Involved in the synthesis of trypanothione in trypanosomatids. The enzyme from Escherichia coli is bifunctional and also catalyses the glutathionylspermidine amidase (EC 3.5.1.78) reaction, resulting in a net hydrolysis of ATP.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9077-09-2
References:
1. Smith, K., Nadeau, K., Bradley, M., Walsh, C.T., Fairlamb, A.H. Purification of glutathionylspermidine and trypanothione synthase from Crithidia fasciculata. Protein Sci. 1 (1992) 874-883. [PMID: 1304372]
2. Bollinger, J.M., Kwon, D.S., Huisman, G.W., Kolter, R., Walsh, C.T. Glutathionylspermidine metabolism in E. coli. Purification, cloning, overproduction and characterization of a bifunctional glutathionyl spermidine synthetase/amidase. J. Biol. Chem. 270 (1995) 14031-14041. [PMID: 7775463]
Accepted name: trypanothione synthase
Reaction: (1) glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate
(2) glutathione + glutathionylspermidine + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
For diagram of reaction click here.
Glossary: N1,N8-bis(glutathionyl)spermidine = trypanothione
Other name(s): glutathionylspermidine:glutathione ligase (ADP-forming)
Systematic name: spermidine/glutathionylspermidine:glutathione ligase (ADP-forming)
Comments: The enzyme, characterized from several trypanosomatids (e.g. Trypanosoma cruzi) catalyses two subsequent reactions, leading to production of trypanothione from glutathione and spermidine. Some trypanosomatids (e.g. Crithidia species and some Leishmania species) also contain an enzyme that only carries out the first reaction (cf. EC 6.3.1.8, glutathionylspermidine synthase). The enzyme is bifunctional, and also catalyses the hydrolysis of glutathionylspermidine and trypanothione (cf. EC 3.5.1.78, glutathionylspermidine amidase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 130246-69-4
References:
1. Smith, K., Nadeau, K., Bradley, M., Walsh, C.T., Fairlamb, A.H. Purification of glutathionylspermidine and trypanothione synthase from Crithidia fasciculata. Protein Sci. 1 (1992) 874-883. [PMID: 1304372]
2. Oza, S.L., Tetaud, E., Ariyanayagam, M.R., Warnon, S.S. and Fairlamb, A.H. A single enzyme catalyses formation of trypanothione from glutathione and spermidine in Trypanosoma cruzi. J. Biol. Chem. 277 (2002) 35853-35861. [PMID: 12121990]
3. Comini, M., Menge, U., Wissing, J. and Flohe, L. Trypanothione synthesis in crithidia revisited. J. Biol. Chem. 280 (2005) 6850-6860. [PMID: 15537651]
4. Oza, S.L., Shaw, M.P., Wyllie, S. and Fairlamb, A.H. Trypanothione biosynthesis in Leishmania major. Mol. Biochem. Parasitol. 139 (2005) 107-116. [PMID: 15610825]
5. Fyfe, P.K., Oza, S.L., Fairlamb, A.H. and Hunter, W.N. Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities. J. Biol. Chem. 283 (2008) 17672-17680. [PMID: 18420578]
Accepted name: adenosylcobinamide-phosphate synthase
Reaction: (1) ATP + adenosylcobyric acid + (R)-1-aminopropan-2-yl phosphate = ADP + phosphate + adenosylcobinamide phosphate
(2) ATP + adenosylcobyric acid + (R)-1-aminopropan-2-ol = ADP + phosphate + adenosylcobinamide
For diagram click here.
Other name(s): CbiB
Systematic name: adenosylcobyric acid:(R)-1-aminopropan-2-yl phosphate ligase (ADP-forming)
Comments: One of the substrates for this reaction, (R)-1-aminopropan-2-yl phosphate, is produced by CobD (EC 4.1.1.81, threonine-phosphate decarboxylase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 905988-16-1
References:
1. Cheong, C.G., Bauer, C.B., Brushaber, K.R., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica. Biochemistry 41 (2002) 4798-4808. [PMID: 11939774]
2. Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390-412. [PMID: 12195810]
Accepted name: glutamate—putrescine ligase
Reaction: ATP + L-glutamate + putrescine = ADP + phosphate + γ-L-glutamylputrescine
Other name(s): γ-glutamylputrescine synthetase; YcjK
Systematic name: L-glutamate:putrescine ligase (ADP-forming)
Comments: Forms part of a novel bacterial putrescine utilization pathway in Escherichia coli.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 914090-78-1
References:
1. Kurihara, S., Oda, S., Kato, K., Kim, H.G., Koyanagi, T., Kumagai, H. and Suzuki, H. A novel putrescine utilization pathway involves γ-glutamylated intermediates of Escherichia coli K-12. J. Biol. Chem. 280 (2005) 4602-4608. [PMID: 15590624]
Accepted name: D-aspartate ligase
Reaction: ATP + D-aspartate + [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n = [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-6-N-(β-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate
For diagram click here.
Other name(s): Aslfm; UDP-MurNAc-pentapeptide:D-aspartate ligase; D-aspartic acid-activating enzyme
Systematic name: D-aspartate:[β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming)
Comments: This enzyme forms part of the peptidoglycan assembly pathway of Gram-positive bacteria grown in medium containing D-Asp. Normally, the side chains the acylate the 6-amino group of the L-lysine residue contain L-Ala-L-Ala but these amino acids are replaced by D-Asp when D-Asp is included in the medium. Hybrid chains containing L-Ala-D-Asp, L-Ala-L-Ala-D-Asp or D-Asp-L-Ala are not formed [4]. The enzyme belongs in the ATP-grasp protein superfamily [3,4]. The enzyme is highly specific for D-aspartate, as L-aspartate, D-glutamate, D-alanine, D-iso-asparagine and D-malic acid are not substrates [4]. In Enterococcus faecium, the substrate D-aspartate is produced by EC 5.1.1.13, aspartate racemase [4]
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Staudenbauer, W. and Strominger, J.L. Activation of D-aspartic acid for incorporation into peptidoglycan. J. Biol. Chem. 247 (1972) 5095-5102. [PMID: 4262567]
2. Staudenbauer, W., Willoughby, E. and Strominger, J.L. Further studies of the D-aspartic acid-activating enzyme of Streptococcus faecalis and its attachment to the membrane. J. Biol. Chem. 247 (1972) 5289-5296. [PMID: 4626717]
3. Galperin, M.Y. and Koonin, E.V. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci. 6 (1997) 2639-2643. [PMID: 9416615]
4. Bellais, S., Arthur, M., Dubost, L., Hugonnet, J.E., Gutmann, L., van Heijenoort, J., Legrand, R., Brouard, J.P., Rice, L. and Mainardi, J.L. Aslfm, the D-aspartate ligase responsible for the addition of D-aspartic acid onto the peptidoglycan precursor of Enterococcus faecium. J. Biol. Chem. 281 (2006) 11586-11594. [PMID: 16510449]
Accepted name: L-cysteine:1D-myo-inositol 2-amino-2-deoxy-α-D-glucopyranoside ligase
Reaction: 1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP = 1-O-[2-(L-cysteinamido)-2-deoxy-α-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate
Glossary: mycothiol = 1-O-[2-(N2-acetyl-L-cysteinamido)-2-deoxy--D-glucopyranosyl]-1D-myo-inositol
Other name(s): MshC; MshC ligase; Cys:GlcN-Ins ligase; mycothiol ligase
Systematic name: L-cysteine:1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol ligase (AMP-forming)
Comments: This enzyme is a key enzyme in the biosynthesis of mycothiol, a small molecular weight thiol found in Mycobacteria spp. and other actinomycetes. Mycothiol plays a fundamental role in these organisms by helping to provide protection from the effects of reactive oxygen species and electrophiles, including many antibiotics. The enzyme may represent a novel target for new classes of antituberculars [2]
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Fan, F., Luxenburger, A., Painter, G.F. and Blanchard, J.S. Steady-state and pre-steady-state kinetic analysis of Mycobacterium smegmatis cysteine ligase (MshC). Biochemistry 46 (2007) 11421-11429. [PMID: 17848100]
2. Gutierrez-Lugo, M.T., Newton, G.L., Fahey, R.C. and Bewley, C.A. Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis. Protein Expr. Purif. 50 (2006) 128-136. [PMID: 16908186]
3. Tremblay, L.W., Fan, F., Vetting, M.W. and Blanchard, J.S. The 1.6 Å crystal structure of Mycobacterium smegmatis MshC: the penultimate enzyme in the mycothiol biosynthetic pathway. Biochemistry 47 (2008) 13326-13335. [PMID: 19053270]
Accepted name: diphthine—ammonia ligase
Reaction: ATP + diphthine-[translation elongation factor 2] + NH3 = AMP + diphosphate + diphthamide-[translation elongation factor 2]
For diagram of reaction click here.
Glossary: translation elongation factor 2 = EF2 = eEF2
diphthine = 2-[(3S)-3-carboxy-3-(trimethylammonio)propyl]-L-histidine
diphthamide =2-[(3S)-3-carbamoyl-3-(trimethylammonio)propyl]-L-histidine
Other name(s): diphthamide synthase; diphthamide synthetase; DPH6 (gene name); ATPBD4 (gene name)
Systematic name: diphthine-[translation elongation factor 2]:ammonia ligase (AMP-forming)
Comments: This amidase catalyses the last step in the conversion of an L-histidine residue in the translation elongation factor EF2 to diphthamide. This factor is found in all archaea and eukaryota, but not in eubacteria, and is the target of bacterial toxins such as the diphtheria toxin and the Pseudomonas exotoxin A (see EC 2.4.2.36, NAD+—diphthamide ADP-ribosyltransferase). The substrate of the enzyme, diphthine, is produced by EC 2.1.1.98, diphthine synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 114514-33-9
References:
1. Moehring, T.J. and Moehring, J.M. Mutant cultured cells used to study the synthesis of diphthamide. UCLA Symp. Mol. Cell. Biol. New Ser. 45 (1987) 53-63.
2. Moehring, J.M. and Moehring, T.J. The post-translational trimethylation of diphthamide studied in vitro. J. Biol. Chem. 263 (1988) 3840-3844. [PMID: 3346227]
3. Su, X., Lin, Z., Chen, W., Jiang, H., Zhang, S. and Lin, H. Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc. Natl. Acad. Sci. USA 109 (2012) 19983-19987. [PMID: 23169644]
Accepted name: 8-demethylnovobiocic acid synthase
Reaction: ATP + 4-hydroxy-3-prenylbenzoate + 3-amino-4,7-dihydroxycoumarin = AMP + diphosphate + 8-demethylnovobiocic acid
For diagram of reaction click here.
Glossary: 8-demethylnovobiocic acid = N-(2,7-dihydroxy-4-oxochromen-3-yl)-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide
Other name(s): novL (gene name); novobiocin ligase; novobiocic acid synthetase (misleading); 8-desmethyl-novobiocic acid synthetase; 8-demethylnovobiocic acid synthetase; 3-dimethylallyl-4-hydroxybenzoate:3-amino-4,7-dihydroxycoumarin ligase (AMP-forming)
Systematic name: 4-hydroxy-3-prenylbenzoate:3-amino-4,7-dihydroxycoumarin ligase (AMP-forming)
Comments: The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Steffensky, M., Li, S.M. and Heide, L. Cloning, overexpression, and purification of novobiocic acid synthetase from Streptomyces spheroides NCIMB 11891. J. Biol. Chem. 275 (2000) 21754-21760. [PMID: 10801869]
2. Pi, N., Meyers, C.L., Pacholec, M., Walsh, C.T. and Leary, J.A. Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton. Proc. Natl. Acad. Sci. USA 101 (2004) 10036-10041. [PMID: 15218104]
3. Pacholec, M., Tao, J. and Walsh, C.T. CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry 44 (2005) 14969-14976. [PMID: 16274243]
[EC 6.3.1.16 Transferred entry: carbapenam-3-carboxylate synthetase. The enzyme was discovered at the public-review stage to have been misclassified and so was withdrawn. See EC 6.3.3.6, carbapenam-3-carboxylate synthase (EC 6.3.1.16 created 2013, deleted 2013)]
Accepted name: β-citrylglutamate synthase
Reaction: ATP + citrate + L-glutamate = ADP + phosphate + β-citryl-L-glutamate
Other name(s): NAAG synthetase I; NAAGS-I; RIMKLB (gene name) (ambiguous)
Systematic name: citrate:L-glutamate ligase (ADP-forming)
Comments: The enzyme, found in animals, also has the activity of EC 6.3.2.41, N-acetylaspartylglutamate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Collard, F., Stroobant, V., Lamosa, P., Kapanda, C.N., Lambert, D.M., Muccioli, G.G., Poupaert, J.H., Opperdoes, F. and Van Schaftingen, E. Molecular identification of N-acetylaspartylglutamate synthase and β-citrylglutamate synthase. J. Biol. Chem. 285 (2010) 29826-29833. [PMID: 20657015]
Accepted name: γ-glutamylanilide synthase
Reaction: ATP + L-glutamate + aniline = ADP + phosphate + N5-phenyl-L-glutamine
Glossary: γ-glutamylanilide = N5-phenyl-L-glutamine
Other name(s): atdA1 (gene name); tdnQ (gene name); dcaQ (gene name)
Systematic name: L-glutamate:aniline ligase (ADP-forming)
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Acinetobacter sp. YAA, catalyses the first step in the degradation of aniline. It can also accept chlorinated and methylated forms of aniline, preferrably in the o- and p-positions.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, CAS registry number:
References:
1. Takeo, M., Ohara, A., Sakae, S., Okamoto, Y., Kitamura, C., Kato, D. and Negoro, S. Function of a glutamine synthetase-like protein in bacterial aniline oxidation via γ-glutamylanilide. J. Bacteriol. 195 (2013) 4406-4414. [PMID: 23893114]
Accepted name: prokaryotic ubiquitin-like protein ligase
Reaction: ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine = ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-γ-L-glutamyl)-[protein]-L-lysine
Other name(s): PafA (ambiguous); Pup ligase; proteasome accessory factor A
Systematic name: [prokaryotic ubiquitin-like protein]:[protein]-L-lysine
Comments: The enzyme has been characterized from the bacteria Mycobacterium tuberculosis and Corynebacterium glutamicum. It catalyses the ligation of the prokaryotic ubiquitin-like protein (Pup) to a target protein by forming a bond between an ε-amino group of a lysine residue of the target protein and the γ-carboxylate of the C-terminal glutamate of the ubiquitin-like protein (Pup). The attachment of Pup, also known as Pupylation, marks proteins for proteasomal degradation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Sutter, M., Damberger, F.F., Imkamp, F., Allain, F.H. and Weber-Ban, E. Prokaryotic ubiquitin-like protein (Pup) is coupled to substrates via the side chain of its C-terminal glutamate. J. Am. Chem. Soc. 132 (2010) 5610-5612. [PMID: 20355727]
2. Guth, E., Thommen, M. and Weber-Ban, E. Mycobacterial ubiquitin-like protein ligase PafA follows a two-step reaction pathway with a phosphorylated pup intermediate. J. Biol. Chem. 286 (2011) 4412-4419. [PMID: 21081505]
3. Ofer, N., Forer, N., Korman, M., Vishkautzan, M., Khalaila, I. and Gur, E. Allosteric transitions direct protein tagging by PafA, the prokaryotic ubiquitin-like protein (Pup) ligase. J. Biol. Chem. 288 (2013) 11287-11293. [PMID: 23471967]
4. Barandun, J., Delley, C.L., Ban, N. and Weber-Ban, E. Crystal structure of the complex between prokaryotic ubiquitin-like protein and its ligase PafA. J. Am. Chem. Soc. 135 (2013) 6794-6797. [PMID: 23601177]
5. Striebel, F., Imkamp, F., Özcelik, D. and Weber-Ban, E. Pupylation as a signal for proteasomal degradation in bacteria. Biochim. Biophys. Acta 1843 (2014) 103-113. [PMID: 23557784]
Accepted name: lipoate—protein ligase
Reaction: ATP + (R)-lipoate + a [lipoyl-carrier protein]-L-lysine = a [lipoyl-carrier protein]-N6-(lipoyl)lysine + AMP + diphosphate (overall reaction)
(1a) ATP + (R)-lipoate = lipoyl-AMP + diphosphate
(1b) lipoyl-AMP + a [lipoyl-carrier protein]-L-lysine = a [lipoyl-carrier protein]-N6-(lipoyl)lysine + AMP
Other name(s): lplA (gene name); lplJ (gene name); lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B
Systematic name: [lipoyl-carrier protein]-L-lysine:lipoate ligase (AMP-forming)
Comments: Requires Mg2+. This enzyme participates in lipoate salvage, and is responsible for lipoylation in the presence of exogenous lipoic acid [7]. The enzyme attaches lipoic acid to the lipoyl domains of certain 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]. Lipoylation is essential for the function of these enzymes. The enzyme can also use octanoate instead of lipoate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, 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]
7. 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]
Accepted name: phosphoribosylglycinamide formyltransferase 2
Reaction: ATP + formate + N1-(5-phospho-β-D-ribosyl)glycinamide = ADP + phosphate + N2-formyl-N1-(5-phospho-β-D-ribosyl)glycinamide
Other name(s): purT (gene name); GAR transformylase 2; GART2; glycinamide ribonucleotide transformylase 2; 5'-phosphoribosylglycinamide transformylase 2; GAR transformylase T
Systematic name: formate:N1-(5-phospho-β-D-ribosyl)glycinamide ligase (ADP-forming)
Comments: Two enzymes are known to catalyse the third step in de novo purine biosynthesis. This enzyme requires ATP and utilizes formate, which is provided by the hydrolysis of 10-formyltetrahydrofolate by EC 3.5.1.10, formyltetrahydrofolate deformylase. The other enzyme, EC 2.1.2.2, phosphoribosylglycinamide formyltransferase 1, utilizes 10-formyltetrahydrofolate directly. Formyl phosphate is formed during catalysis as an intermediate. The enzyme from the bacterium Escherichia coli can also catalyse the activity of EC 2.7.2.1, acetate kinase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Nagy, P.L., McCorkle, G.M. and Zalkin, H. purU, a source of formate for purT-dependent phosphoribosyl-N-formylglycinamide synthesis. J. Bacteriol. 175 (1993) 7066-7073. [PMID: 8226647]
2. Nygaard, P. and Smith, J.M. Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli. J. Bacteriol. 175 (1993) 3591-3597. [PMID: 8501063]
3. Marolewski, A., Smith, J.M. and Benkovic, S.J. Cloning and characterization of a new purine biosynthetic enzyme: a non-folate glycinamide ribonucleotide transformylase from E. coli. Biochemistry 33 (1994) 2531-2537. [PMID: 8117714]
4. Marolewski, A.E., Mattia, K.M., Warren, M.S. and Benkovic, S.J. Formyl phosphate: a proposed intermediate in the reaction catalyzed by Escherichia coli PurT GAR transformylase. Biochemistry 36 (1997) 6709-6716. [PMID: 9184151]
5. Thoden, J.B., Firestine, S., Nixon, A., Benkovic, S.J. and Holden, H.M. Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase. Biochemistry 39 (2000) 8791-8802. [PMID: 10913290]
6. Jelsbak, L., Mortensen, M.IB., Kilstrup, M. and Olsen, J.E. The in vitro redundant enzymes PurN and PurT are both essential for systemic infection of mice in Salmonella enterica serovar Typhimurium. Infect. Immun. 84 (2016) 2076-2085. [PMID: 27113361]
Accepted name: tRNAmet cytidine acetate ligase
Reaction: ATP + [elongator tRNAMet]-cytidine34 + acetate = AMP + diphosphate + [elongator tRNAMet]-N4-acetylcytidine34 (overall reaction)
(1a) ATP + acetate = acetyladenylate + diphosphate
(1b) acetyladenylate + [elongator tRNAMet]-cytidine34 = AMP + [elongator tRNAMet]-N4-acetylcytidine34
Other name(s): tmcAL (gene name)
Systematic name: elongator tRNAmet cytidine:acetate ligase (AMP-forming)
Comments: The enzyme, charactrized from the bacterium Bacillus subtilis, catalyses a similar tRNA modification to that performed by EC 2.3.1.193, tRNAMet cytidine acetyltransferase. However, unlike that enzyme, which uses acetyl-CoA as the acetyl donor, this enzyme activates an acetate ion to form acetyladenylate and then catalyses the acetylation through a mechanism similar to tRNA aminoacylation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Taniguchi, T., Miyauchi, K., Sakaguchi, Y., Yamashita, S., Soma, A., Tomita, K. and Suzuki, T. Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis. Nat. Chem. Biol. 14 (2018) 1010-1020. [PMID: 30150682]
Accepted name: pantoate—β-alanine ligase (AMP-forming)
Reaction: ATP + (R)-pantoate + β-alanine = AMP + diphosphate + (R)-pantothenate
For diagram of reaction click here.
Glossary: (R)-pantoate = (2R)-2,4-dihydroxy-3,3-dimethylbutanoate
(R)-pantothenate = 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate
Other name(s): pantothenate synthetase; pantoate activating enzyme; pantoic-activating enzyme; D-pantoate:β-alanine ligase (AMP-forming); pantoate—β-alanine ligase (ambiguous)
Systematic name: (R)-pantoate:β-alanine ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-49-8
References:
1. Ginoza, H.S. and Altenbern, R.A. The pantothenate-synthesizing enzyme cell-free extracts of Brucella abortus, strain 19. Arch. Biochem. Biophys. 56 (1955) 537-541. [PMID: 14377603]
2. Maas, W.K. Pantothenate studies. III. Description of the extracted pantothenate-synthesizing enzyme of Escherichia coli. J. Biol. Chem. 198 (1952) 23-32. [PMID: 12999714]
3. Maas, W.K. Mechanism of the enzymatic synthesis of pantothenate from β-alanine and pantoate. Fed. Proc. 15 (1956) 305-306.
Accepted name: glutamate—cysteine ligase
Reaction: ATP + L-glutamate + L-cysteine = ADP + phosphate + γ-L-glutamyl-L-cysteine
For diagram of reaction click here.
Other name(s): γ-glutamylcysteine synthetase; γ-glutamyl-L-cysteine synthetase; γ-glutamylcysteinyl synthetase
Systematic name: L-glutamate:L-cysteine γ-ligase (ADP-forming)
Comments: Can use L-aminohexanoate in place of glutamate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-64-7
References:
1. Mackinnon, C.M., Carter, P.E., Smyth, S.J., Dunbar, B. and Fothergill, J.E. Molecular-cloning of cDNA for human-complement component c1s - the complete amino-acid sequence. Eur. J. Biochem. 169 (1987) 547-553.
2. Snoke, J.E., Yanari, S. and Bloch, K. Synthesis of glutathione from γ-glutamylcysteine. J. Biol. Chem. 201 (1953) 573-586.
3. Mandeles, S. and Bloch, K. Enzymatic synthesis of γ-glutamylcysteine. J. Biol. Chem. 214 (1955) 639-646.
Accepted name: glutathione synthase
Reaction: ATP + γ-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione
For diagram of reaction click here.
Other name(s): glutathione synthetase; GSH synthetase
Systematic name: γ-L-glutamyl-L-cysteine:glycine ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-62-5
References:
1. Law, M.Y. and Halliwell, B. Purification and properties of glutathione synthetase from (Spinacia oleracea) leaves. Plant Sci. 43 (1986) 185-191.
2. Macnicol, P.K. Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity. Plant Sci. 53 (1987) 229-235.
Accepted name: D-alanine—D-alanine ligase
Reaction: ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanine
For diagram click here.
Other name(s): MurE synthetase [ambiguous]; alanine:alanine ligase (ADP-forming); alanylalanine synthetase
Systematic name: D-alanine:D-alanine ligase (ADP-forming)
Comments: Involved with EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate—L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-63-6
References:
1. Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. II. Enzymatic synthesis and addition of D-alanyl-D-alanine. J. Biol. Chem. 237 (1962) 2696-2703.
2. Neuhaus, F.C. Kinetic studies on D-Ala-D-Ala synthetase. Fed. Proc. 21 (1962) 229 only.
3. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: phosphopantothenate—cysteine ligase (CTP)
Reaction: CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
For diagram of reaction click here.
Other name(s): phosphopantothenoylcysteine synthetase; phosphopantothenate—cysteine ligase
Systematic name: (R)-4'-phosphopantothenate:L-cysteine ligase
Comments: A key enzyme in the production of coenzyme A. The bacterial enzyme requires CTP, in contrast to the eukaryotic enzyme, EC 6.3.2.51, which requires ATP. Cysteine can be replaced by some of its derivatives.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-50-1
References:
1. Brown, G.M. The metabolism of pantothenic acid. J. Biol. Chem. 234 (1959) 370-378. [PMID: 13630913]
2. Strauss, E., Kinsland, C., Ge, Y., McLafferty, F.W. and Begley, T.P. Phosphopantothenoylcysteine synthetase from Escherichia coli. Identification and characterization of the last unidentified Coenzyme A biosynthetic enzymes in bacteria. J. Biol. Chem. 276 (2001) 13513-13516. [PMID: 11278255]
3. Kupke, T. Molecular characterization of the 4'-phosphopantothenoylcysteine synthetase domain of bacterial Dfp flavoproteins. J. Biol. Chem. 277 (2002) 36137-36145. [PMID: 12140293]
Accepted name: phosphoribosylaminoimidazolesuccinocarboxamide synthase
Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
For diagram, click here
Other name(s): phosphoribosylaminoimidazole-succinocarboxamide synthetase; PurC; SAICAR synthetase; 4-(N-succinocarboxamide)-5-aminoimidazole synthetase; 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide synthetase; SAICARs; 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase; phosphoribosylaminoimidazolesuccinocarboxamide synthetase; 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase
Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming)
Comments: Forms part of the purine biosynthesis pathway.
Links to other databases: BRENDA, EXPASY,KEGG, Metacyc, PDB, CAS registry number: 9023-67-0
References:
1. Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5-amino-1-ribosyl-4-imidazolecarboxylic acid 5'-phosphate from 5-amino-1-ribosylimidazole 5'-phosphate and carbon dioxide. J. Biol. Chem. 234 (1959) 1799-1805. [PMID: 13672967]
2. Parker, J. Identification of the purC gene product of Escherichia coli. J. Bacteriol. 157 (1984) 712-717. [PMID: 6365889]
3. Ebbole, D.J. and Zalkin, H. Cloning and characterization of a 12-gene cluster from Bacillus subtilis encoding nine enzymes for de novo purine nucleotide synthesis. J. Biol. Chem. 262 (1987) 8274-8287. [PMID: 3036807]
4. Chen, Z.D., Dixon, J.E. and Zalkin, H. Cloning of a chicken liver cDNA encoding 5-aminoimidazole ribonucleotide carboxylase and 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase by functional complementation of Escherichia coli pur mutants. Proc. Natl. Acad. Sci. USA 87 (1990) 3097-3101. [PMID: 1691501]
5. O'Donnell, A.F., Tiong, S., Nash, D. and Clark, D.V. The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway. Genetics 154 (2000) 1239-1253. [PMID: 10757766]
6. Nelson, S.W., Binkowski, D.J., Honzatko, R.B. and Fromm, H.J. Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase. Biochemistry 44 (2005) 766-774. [PMID: 15641804]
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + L-lysine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-L-lysine
For diagram click here.
Other name(s): MurE synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine synthetase; uridine diphospho-N-acetylmuramoylalanyl-D-glutamyllysine synthetase; UPD-MurNAc-L-Ala-D-Glu:L-Lys ligase
Systematic name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine γ-ligase (ADP-forming)
Comments: Involved with EC 6.3.2.4 (D-alanine—D-alanine ligase), EC 6.3.2.8 (UDP-N-acetylmuramate—L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram). This enzyme adds lysine in some Gram-positive organisms; in others and in Gram-negative organisms EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase) adds 2,6-diaminopimelate instead.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-51-2
References:
1. Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689-2695.
2. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: UDP-N-acetylmuramate—L-alanine ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramate + L-alanine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanine
For diagram click here.
Other name(s): MurC synthetase; UDP-N-acetylmuramoyl-L-alanine synthetase; uridine diphospho-N-acetylmuramoylalanine synthetase; UDP-N-acetylmuramoylalanine synthetase; L-alanine-adding enzyme; UDP-acetylmuramyl-L-alanine synthetase; UDPMurNAc-L-alanine synthetase; L-Ala ligase; uridine diphosphate N-acetylmuramate:L-alanine ligase; uridine 5'-diphosphate-N-acetylmuramyl-L-alanine synthetase; uridine-diphosphate-N-acetylmuramate:L-alanine ligase; UDP-MurNAc:L-alanine ligase; alanine-adding enzyme; UDP-N-acetylmuramyl:L-alanine ligase
Systematic name: UDP-N-acetylmuramate:L-alanine ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-52-3
References:
1. Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689-2695.
2. Nathenson, S.G., Strominger, J.L. and Ito, E. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. IV. Purification and properties of D-glutamic acid-adding enzyme. J. Biol. Chem. 239 (1964) 1773-1776.
3. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate
For diagram click here.
Other name(s): MurD synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate synthetase; uridine diphospho-N-acetylmuramoylalanyl-D-glutamate synthetase; D-glutamate-adding enzyme; D-glutamate ligase; UDP-Mur-NAC-L-Ala:D-Glu ligase; UDP-N-acetylmuramoyl-L-alanine:glutamate ligase (ADP-forming); UDP-N-acetylmuramoylalanine—D-glutamate ligase
Systematic name: UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-59-0
References:
1. Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689-2695.
2. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase
Reaction: ATP + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-L-lysine + D-alanyl-D-alanine = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-L-lysyl-D-alanyl-D-alanine
For diagram click here.
Other name(s): MurF synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine synthetase; UDP-N-acetylmuramoylalanyl-D-glutamyl-lysine-D-alanyl-D-alanine ligase; uridine diphosphoacetylmuramoylpentapeptide synthetase; UDPacetylmuramoylpentapeptide synthetase; UDP-MurNAc-L-Ala-D-Glu-L-Lys:D-Ala-D-Ala ligase
Systematic name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine:D-alanyl-D-alanine ligase (ADP-forming)
Comments: Involved with EC 6.3.2.4 (D-alanine—D-alanine ligase), EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate—L-alanine ligase) and EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase) in the synthesis of a cell-wall peptide (click here for diagram). This enzyme also catalyses the reaction when the C-terminal residue of the tripeptide is meso-2,6-diaminoheptanedioate (acylated at its L-centre), linking the D-Ala-D-Ala to the carboxy group of the L-centre. This activity was previously attributed to EC 6.3.2.15, which has since been deleted.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 55354-36-4
References:
1. Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. II. Enzymatic synthesis and addition of D-alanyl-D-alanine. J. Biol. Chem. 237 (1962) 2696-2703.
2. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: carnosine synthase
Reaction: ATP + L-histidine + β-alanine = ADP + phosphate + carnosine
Glossary: carnosine = N-β-alanyl-L-histidine
Other name(s): carnosine synthetase; carnosine-anserine synthetase; homocarnosine-carnosine synthetase; carnosine-homocarnosine synthetase; L-histidine:β-alanine ligase (AMP-forming) (incorrect)
Systematic name: L-histidine:β-alanine ligase (ADP-forming)
Comments: This enzyme was thought to form AMP [1,2], but studies with highly purified enzyme proved that it forms ADP [4]. Carnosine is a dipeptide that is present at high concentrations in skeletal muscle and the olfactory bulb of vertebrates [3]. It is also found in the skeletal muscle of some invertebrates. The enzyme can also catalyse the formation of homocarnosine from 4-aminobutanoate and L-histidine, with much lower activity [4].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9023-61-4
References:
1. Kalyankar, G.D. and Meister, A. Enzymatic synthesis of carnosine and related β-alanyl and γ-aminobutyryl peptides. J. Biol. Chem. 234 (1959) 3210-3218. [PMID: 14404206]
2. Stenesh, J.J. and Winnick, T. Carnosine-anserine synthetase of muscle. 4. Partial purification of the enzyme and further studies of β-alanyl peptide synthesis. Biochem. J. 77 (1960) 575-581. [PMID: 16748858]
3. Crush, K.G. Carnosine and related substances in animal tissues. Comp. Biochem. Physiol. 34 (1970) 3-30. [PMID: 4988625]
4. Drozak, J., Veiga-da-Cunha, M., Vertommen, D., Stroobant, V. and Van Schaftingen, E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J. Biol. Chem. 285 (2010) 9346-9356. [PMID: 20097752]
Accepted name: dihydrofolate synthase
Reaction: ATP + 7,8-dihydropteroate + L-glutamate = ADP + phosphate + 7,8-dihydropteroylglutamate
For diagram of reaction click here.
Other name(s): dihydrofolate synthetase; 7,8-dihydrofolate synthetase; H2-folate synthetase; 7,8-dihydropteroate:L-glutamate ligase (ADP); dihydropteroate:L-glutamate ligase (ADP-forming); DHFS
Systematic name: 7,8-dihydropteroate:L-glutamate ligase (ADP-forming)
Comments: In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.17, tetrahydrofolate synthase [2], the combined activity of which leads to the formation of the cofactor polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates. In contrast, the activities are located on separate proteins in most eukaryotes studied to date [3]. This enzyme is reponsible for attaching the first glutamate residue to dihydropteroate to form dihydrofolate and is present only in those organisms that have the ability to synthesize tetrahydrofolate de novo, e.g. plants, most bacteria, fungi and protozoa [3].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-62-0
References:
1. Griffin, M.J. and Brown, G.M. The biosynthesis of folic acid. III. Enzymatic formation of dihydrofolic acid from dihydropteroic acid and of tetrahydropteroylpolyglutamic acid compounds from tetrahydrofolic acid. J. Biol. Chem. 239 (1964) 310-316. [PMID: 14114858]
2. Bognar, A.L., Osborne, C., Shane, B., Singer, S.C. and Ferone, R. Folylpoly-γ-glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product. J. Biol. Chem. 260 (1985) 5625-5630. [PMID: 2985605]
3. Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R. and Rébeillé, F. Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 98 (2001) 15360-15365. [PMID: 11752472]
4. Cherest, H., Thomas, D. and Surdin-Kerjan, Y. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. J. Biol. Chem. 275 (2000) 14056-14063. [PMID: 10799479]
5. Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437-452. [PMID: 9190084]
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate
For diagram of reaction, click here.
Other name(s): MurE synthetase [ambiguous]; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diamino-heptanedioate ligase (ADP-forming); UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelate synthetase; UDP-N-acetylmuramoylalanyl-D-glutamate—2,6-diaminopimelate ligase
Systematic name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diaminoheptanedioate γ-ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria. This enzyme adds diaminopimelate in Gram-negative organisms and in some Gram-positive organisms; in others EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) adds lysine instead. It is the amino group of the L-centre of the diaminopimelate that is acylated.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9075-09-6
References:
1. Mizuno, Y. and Ito, E. Purification and properties of uridine diphosphate N-acetylmuramyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate ligase. J. Biol. Chem. 243 (1968) 2665-2672. [PMID: 4967958]
2. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503-519. [PMID: 11699883]
Accepted name: enterobactin synthase
Reaction: 6 ATP + 3 2,3-dihydroxybenzoate + 3 L-serine = enterobactin + 6 AMP + 6 diphosphate
For diagram of reaction click here.
Other name(s): N-(2,3-dihydroxybenzoyl)-serine synthetase; 2,3-dihydroxybenzoylserine synthetase; 2,3-dihydroxybenzoate—serine ligase
Systematic name: 2,3-dihydroxybenzoate:L-serine ligase
Comments: This enzyme complex catalyses the conversion of three molecules each of 2,3-dihydroxybenzoate and L-serine to form the siderophore enterobactin. In Escherichia coli the complex is formed by EntB (an aryl carrier protein that has to be activated by 4'-phosphopantetheine), EntD (a phosphopantetheinyl transferase that activates EntB), EntE (catalyses the ATP-dependent condensation of 2,3-dihydroxybenzoate and holo-EntB to form the covalently arylated form of EntB), and EntF (a four domain protein that catalyses the activation of L-serine by ATP, the condensation of the activated L-serine with the activated 2,3-dihydroxybenzoate, and the trimerization of three such moieties to a single enterobactin molecule).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-63-1
References:
1. Brot, N. and Goodwin, J. Regulation of 2,3-dihydroxybenzoylserine synthetase by iron. J. Biol. Chem. 243 (1968) 510-513. [PMID: 4966114]
2. Rusnak, F., Faraci, W.S. and Walsh, C.T. Subcloning, expression, and purification of the enterobactin biosynthetic enzyme 2,3-dihydroxybenzoate-AMP ligase: demonstration of enzyme-bound (2,3-dihydroxybenzoyl)adenylate product. Biochemistry 28 (1989) 6827-6835. [PMID: 2531000]
3. Rusnak, F., Liu, J., Quinn, N., Berchtold, G.A. and Walsh, C.T. Subcloning of the enterobactin biosynthetic gene entB: expression, purification, characterization, and substrate specificity of isochorismatase. Biochemistry 29 (1990) 1425-1435. [PMID: 2139796]
4. Rusnak, F., Sakaitani, M., Drueckhammer, D., Reichert, J. and Walsh, C.T. Biosynthesis of the Escherichia coli siderophore enterobactin: sequence of the entF gene, expression and purification of EntF, and analysis of covalent phosphopantetheine. Biochemistry 30 (1991) 2916-2927. [PMID: 1826089]
5. Gehring, A.M., Mori, I. and Walsh, C.T. Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF. Biochemistry 37 (1998) 2648-2659. [PMID: 9485415]
6. Shaw-Reid, C.A., Kelleher, N.L., Losey, H.C., Gehring, A.M., Berg, C. and Walsh, C.T. Assembly line enzymology by multimodular nonribosomal peptide synthetases: the thioesterase domain of E. coli EntF catalyzes both elongation and cyclolactonization. Chem. Biol. 6 (1999) 385-400. [PMID: 10375542]
[EC 6.3.2.15 Deleted entry: UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase. The activity observed is due to EC 6.3.2.10, UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase. (EC 6.3.2.15 created 1976, deleted 2002)]
Accepted name: D-alanine—alanyl-poly(glycerolphosphate) ligase
Reaction: ATP + D-alanine + alanyl-poly(glycerolphosphate) = ADP + phosphate + D-alanyl-alanyl-poly(glycerolphosphate)
Other name(s): D-alanyl-alanyl-poly(glycerolphosphate) synthetase; D-alanine:membrane-acceptor ligase; D-alanylalanylpoly(phosphoglycerol) synthetase; D-alanyl-poly(phosphoglycerol) synthetase; D-alanine-membrane acceptor-ligase
Systematic name: D-alanine:alanyl-poly(glycerolphosphate) ligase (ADP-forming)
Comments: Involved in the synthesis of teichoic acids.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9046-58-6
References:
1. Reusch, V.M. and Neuhaus, F.C. D-Alanine: membrane acceptor ligase from Lactobacillus casei. J. Biol. Chem. 246 (1971) 6136-6143. [PMID: 4399593]
Accepted name: tetrahydrofolate synthase
Reaction: ATP + tetrahydropteroyl-[γ-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[γ-Glu]n+1
For diagram click here.
Other name(s): folylpolyglutamate synthase; folate polyglutamate synthetase; formyltetrahydropteroyldiglutamate synthetase; N10-formyltetrahydropteroyldiglutamate synthetase; folylpoly-γ-glutamate synthase; folylpolyglutamyl synthetase; folylpoly(γ-glutamate) synthase; folylpolyglutamate synthetase; FPGS; tetrahydrofolylpolyglutamate synthase; tetrahydrofolate:L-glutamate γ-ligase (ADP-forming); tetrahydropteroyl-[γ-Glu]n:L-glutamate γ-ligase (ADP-forming)
Systematic name: tetrahydropteroyl-γ-polyglutamate:L-glutamate γ-ligase (ADP-forming)
Comments: In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.12, dihydrofolate synthase [3], the combined activity of which leads to the formation of the cofactor polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date [4]. In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes [4]. As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in [5]). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 63363-84-8
References:
1. Cichowicz, D., Foo, S.K. and Shane, B. Folylpoly-γ-glutamate synthesis by bacteria and mammalian cells. Mol. Cell. Biochem. 39 (1981) 209-228. [PMID: 6458762]
2. McGuire, J.J. and Bertino, J.R. Enzymatic synthesis and function of folylpolyglutamates. Mol. Cell. Biochem. 38 (1981) 19-48. [PMID: 7027025]
3. Bognar, A.L., Osborne, C., Shane, B., Singer, S.C. and Ferone, R. Folylpoly-γ-glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product. J. Biol. Chem. 260 (1985) 5625-5630. [PMID: 2985605]
4. Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R. and Rébeillé, F. Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 98 (2001) 15360-15365. [PMID: 11752472]
5. Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437-452. [PMID: 9190084]
6. Cherest, H., Thomas, D. and Surdin-Kerjan, Y. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. J. Biol. Chem. 275 (2000) 14056-14063. [PMID: 10799479 ]
Accepted name: γ-glutamylhistamine synthase
Reaction: ATP + L-glutamate + histamine = products of ATP breakdown + Nα-γ-L-glutamylhistamine
Other name(s): γ-glutaminylhistamine synthetase; γ-GHA synthetase
Systematic name: L-glutamate:histamine ligase
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 82904-08-3
References:
1. Stein, C. and Weinreich, D. An in vitro characterization of γ-glutamylhistamine synthetase: a novel enzyme catalyzing histamine metabolism in the central nervous system of the marine mollusk, Aplysia californica. J. Neurochem. 38 (1982) 204-214. [PMID: 6125565]
[EC 6.3.2.19 Deleted entry: ubiquitin—protein ligase. The ubiquitinylation process is now known to be performed by several enzymes in sequence, starting with EC 6.2.1.45 (ubiquitin-activating enzyme E1) and followed by several transfer reactions, including those of EC 2.3.2.23 (E2 ubiquitin-conjugating enzyme) and EC 2.3.2.27 (RING-type E3 ubiquitin transferase) (EC 6.3.2.19 created 1986, deleted 2015)]
Accepted name: indoleacetate—lysine synthetase
Reaction: ATP + (indol-3-yl)acetate + L-lysine = ADP + phosphate + N6-[(indole-3-yl)acetyl]-L-lysine
Other name(s): indoleacetate:L-lysine ligase (ADP-forming)
Systematic name: (indol-3-yl)acetate:L-lysine ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 103537-15-1
References:
1. Glass, N.L. and Kosuge, T. Cloning of the gene for indoleacetic acid-lysine synthetase from Pseudomonas syringae subsp. savastanoi. J. Bacteriol. 166 (1986) 598. [PMID: 3084452]
2. Hutzinger, O. and Kosuge, T. Microbial synthesis and degradation of indole-3-acetic acid. 3. The isolation and characterization of indole-3-acetyl-ε-L-lysine. Biochemistry 7 (1968) 601-605. [PMID: 5644130]
[EC 6.3.2.21 Deleted entry: ubiquitin—calmodulin ligase. The reaction is performed by the sequential action of EC 6.2.1.45 (ubiquitin-activating enzyme E1), several ubiquitin transferases and finally by EC 2.3.2.27 [ubiquitin transferase RING E3 (calmodulin-selective)] (EC 6.3.2.21 created 1990, deleted 2015)]
[EC 6.3.2.22 Transferred entry: diphthine—ammonia ligase. Now EC 6.3.1.14, diphthine—ammonia ligase. (EC 6.3.2.22 created 1990, deleted 2010)]
Accepted name: homoglutathione synthase
Reaction: ATP + γ-L-glutamyl-L-cysteine + β-alanine = ADP + phosphate + γ-L-glutamyl-L-cysteinyl-β-alanine
Other name(s): homoglutathione synthetase; β-alanine specific hGSH synthetase
Systematic name: γ-L-glutamyl-L-cysteine:β-alanine ligase (ADP-forming)
Comments: Not identical with EC 6.3.2.3 glutathione synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 113875-72-2
References:
1. Macnicol, P.K. Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity. Plant Sci. 53 (1987) 229-235.
Accepted name: tyrosine—arginine ligase
Reaction: ATP + L-tyrosine + L-arginine = AMP + diphosphate + L-tyrosyl-L-arginine
Other name(s): tyrosyl-arginine synthase; kyotorphin synthase; kyotorphin-synthesizing enzyme; kyotorphin synthetase
Systematic name: L-tyrosine:L-arginine ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 116036-78-3
References:
1. Ueda, H., Yoshihara, Y., Fukushima, N., Shiomi, H., Nakamura, A. and Takagi, H. Kyotorphin (tyrosine-arginine) synthetase in rat brain synaptosomes. J. Biol. Chem. 262 (1987) 8165-8173. [PMID: 3597366]
Accepted name: tubulin—tyrosine ligase
Reaction: ATP + detyrosinated α-tubulin + L-tyrosine = α-tubulin + ADP + phosphate
Systematic name: α-tubulin:L-tyrosine ligase (ADP-forming)
Comments: L-Tyrosine is linked via a peptide bond to the C-terminus of de-tyrosinated α-tubulin (des-Tyrω-α-tubulin). The enzyme is highly specific for α-tubulin and moderately specific for ATP and L-tyrosine. L-Phenylalanine and 3,4-dihydroxy-L-phenylalanine are transferred but with higher Km values.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 60321-03-1
References:
1. Wehland, J., Schröder, H.C., Weber, K. Isolation and purification of tubulin-tyrosine ligase. Methods Enzymol. 134 (1986) 170-179. [PMID: 3821560]
2. Rudiger, M., Wehland, J., Weber, K. The carboxy-terminal peptide of detyrosinated alpha tubulin provides a minimal system to study the substrate specificity of tubulin-tyrosine ligase. Eur. J. Biochem. 220 (1994) 309-320. [PMID: 7510228]
Accepted name: N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
Reaction: 3 ATP + L-2-aminohexanedioate + L-cysteine + L-valine + H2O = 3 AMP + 3 diphosphate + N-[L-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine
For diagram click here and possible mechanism click here.
Other name(s): L-δ-(α-aminoadipoyl)-L-cysteinyl-D-valine synthetase; ACV synthetase; L-α-aminoadipyl-cysteinyl-valine synthetase
Systematic name: L-2-aminohexanedioate:L-cysteine:L-valine ligase (AMP-forming, valine-inverting)
Comments: Requires Mg2+. The enzyme contains 4'-phosphopantetheine, which may be involved in the mechanism of the reaction. Forms part of the penicillin biosynthesis pathway (for pathway, click here).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 57219-73-5
References:
1. Byford, M.F., Baldwin, J.E., Shiau, C.-Y. and Schofield, C.J. The mechanism of ACV synthetase. Chem. Rev. 97 (1997) 2631-2649. [PMID: 11851475]
2. Theilgaard, H.B., Kristiansen, K.N., Henriksen, C.M. and Nielsen, J. Purification and characterization of δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase from Penicillium chrysogenum. Biochem. J. 327 (1997) 185-191. [PMID: 9355751]
[EC 6.3.2.27 Deleted entry: The activity is covered by two independent enzymes, EC 6.3.2.38 N2-citryl-N6-acetyl-N6-hydroxylysine synthase, and EC 6.3.2.39, aerobactin synthase (EC 6.3.2.27 created 2002, modified 2006, deleted 2012)]
[EC 6.3.2.28 Transferred entry: L-amino-acid α-ligase. Now EC 6.3.2.49, L-alanine-L-anticapsin ligase (EC 6.3.2.28 created 2006, deleted 2015)]
Accepted name: cyanophycin synthase (L-aspartate-adding)
Reaction: ATP + [L-Asp(4-L-Arg)]n + L-Asp = ADP + phosphate + [L-Asp(4-L-Arg)]n—L-Asp
For diagram click here.
Glossary: cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine}
Other name(s): CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous)
Systematic name: cyanophycin:L-aspartate ligase (ADP-forming)
Comments: Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.30, cyanophycin synthase (L-arginine-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297-306. [PMID: 11131019]
2. Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176-2182. [PMID: 11319097]
3. Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687-693. [PMID: 6767688]
4. Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561-5570. [PMID: 10951215]
5. Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522-529. [PMID: 12132696]
6. Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154-159. [PMID: 9652408]
Accepted name: cyanophycin synthase (L-arginine-adding)
Reaction: ATP + [L-Asp(4-L-Arg)]n—L-Asp + L-Arg = ADP + phosphate + [L-Asp(4-L-Arg)]n+1
For diagram click here.
Glossary: cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine}
Other name(s): CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous)
Systematic name: cyanophycin:L-arginine ligase (ADP-forming)
Comments: Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.29, cyanophycin synthase (L-aspartate-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2]. Canavanine and lysine can be incoporated into the polymer instead of arginine [2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297-306. [PMID: 11131019]
2. Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176-2182. [PMID: 11319097]
3. Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687-693. [PMID: 6767688]
4. Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561-5570. [PMID: 10951215]
5. Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522-529. [PMID: 12132696]
6. Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154-159. [PMID: 9652408]
Accepted name: coenzyme F420-0:L-glutamate ligase
Reaction: GTP + coenzyme F420-0 + L-glutamate = GDP + phosphate + coenzyme F420-1
For diagram of reaction, click here
Glossary: coenzyme F420
Other name(s): CofE-AF; MJ0768; CofE
Systematic name: L-glutamate:coenzyme F420-0 ligase (GDP-forming)
Comments: This protein catalyses the successive addition of two glutamate residues to cofactor F420 by two distinct and independent reactions. In the reaction described here the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction (EC 6.3.2.34, coenzyme F420-1—γ-L-glutamate ligase) it catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771-9778. [PMID: 12911320]
2. Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456-469. [PMID: 17669425]
Accepted name: coenzyme γ-F420-2:α-L-glutamate ligase
Reaction: ATP + coenzyme γ-F420-2 + L-glutamate = ADP + phosphate + coenzyme α-F420-3
For diagram of reaction, click here
Other name(s): MJ1001; CofF protein; γ-F420-2:α-L-glutamate ligase
Systematic name: L-glutamate:coenzyme γ-F420-2 (ADP-forming)
Comments: The enzyme caps the γ-glutamyl tail of the hydride carrier coenzyme F420 [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785-9790. [PMID: 12909715]
Accepted name: tetrahydrosarcinapterin synthase
Reaction: ATP + tetrahydromethanopterin + L-glutamate = ADP + phosphate + 5,6,7,8-tetrahydrosarcinapterin
For diagram of reaction click here.
Other name(s): H4MPT:α-L-glutamate ligase; MJ0620; MptN protein
Systematic name: tetrahydromethanopterin:α-L-glutamate ligase (ADP-forming)
Comments: This enzyme catalyses the biosynthesis of 5,6,7,8-tetrahydrosarcinapterin, a modified form of tetrahydromethanopterin found in the Methanosarcinales. It does not require K+, and does not discriminate between ATP and GTP [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785-9790. [PMID: 12909715]
Accepted name: coenzyme F420-1:γ-L-glutamate ligase
Reaction: GTP + coenzyme F420-1 + L-glutamate = GDP + phosphate + coenzyme γ-F420-2
For diagram of coenzyme F420 biosynthesis, click here
Glossary: coenzyme F420 = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate
Other name(s): F420:γ-glutamyl ligase; CofE-AF; MJ0768; CofE
Systematic name: L-glutamate:coenzyme F420-1 ligase (GDP-forming)
Comments: This protein catalyses the successive addition of two glutamate residues to factor 420 (coenzyme F420) by two distinct and independent reactions. In the first reaction (EC 6.3.2.31, coenzyme F420-0:L-glutamate ligase) the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction, which is described here, the enzyme catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771-9778. [PMID: 12911320]
2. Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456-469. [PMID: 17669425]
Accepted name: D-alanine—D-serine ligase
Reaction: D-alanine + D-serine + ATP = D-alanyl-D-serine + ADP + phosphate
Other name(s): VanC; VanE; VanG
Systematic name: D-alanine:D-serine ligase (ADP-forming)
Comments: The product of this enzyme, D-alanyl-D-serine, can be incorporated into the peptidoglycan pentapeptide instead of the usual D-alanyl-D-alanine dipeptide, which is formed by EC 6.3.2.4, D-alanine—D-alanine ligase. The resulting peptidoglycan does not bind the glycopeptide antibiotics vancomycin and teicoplanin, conferring resistance on the bacteria.
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References:
1. Dutka-Malen, S., Molinas, C., Arthur, M. and Courvalin, P. Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance. Gene 112 (1992) 53-58. [PMID: 1551598]
2. Park, I.S., Lin, C.H. and Walsh, C.T. Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase. Proc. Natl. Acad. Sci. USA 94 (1997) 10040-10044. [PMID: 9294159]
3. Fines, M., Perichon, B., Reynolds, P., Sahm, D.F. and Courvalin, P. VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM4405. Antimicrob. Agents Chemother. 43 (1999) 2161-2164. [PMID: 10471558]
4. Depardieu, F., Bonora, M.G., Reynolds, P.E. and Courvalin, P. The vanG glycopeptide resistance operon from Enterococcus faecalis revisited. Mol. Microbiol. 50 (2003) 931-948. [PMID: 14617152]
5. Watanabe, S., Kobayashi, N., Quinones, D., Hayakawa, S., Nagashima, S., Uehara, N. and Watanabe, N. Genetic Diversity of the Low-Level Vancomycin Resistance Gene vanC-2/vanC-3 and Identification of a Novel vanC Subtype (vanC-4) in Enterococcus casseliflavus. Microb. Drug Resist. 15 (2009) 1-9. [PMID: 19216682]
Accepted name: 4-phosphopantoate—β-alanine ligase
Reaction: ATP + (R)-4-phosphopantoate + β-alanine = AMP + diphosphate + (R)-4'-phosphopantothenate
Other name(s): phosphopantothenate synthetase; TK1686 protein
Systematic name: (R)-4-phosphopantoate:β-alanine ligase (AMP-forming)
Comments: The conversion of (R)-pantoate to (R)-4'-phosphopantothenate is part of the pathway leading to biosynthesis of 4'-phosphopantetheine, an essential cofactor of coenzyme A and acyl-carrier protein. In bacteria and eukaryotes this conversion is performed by condensation with β-alanine, followed by phosphrylation (EC 6.3.2.1 [pantoate—β-alanine ligase] and EC 2.7.1.33 [pantothenate kinase], respectively). In archaea the order of these two steps is reversed, and phosphorylation precedes condensation with β-alanine. The two archaeal enzymes that catalyse this conversion are EC 2.7.1.169, pantoate kinase, and this enzyme.
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References:
1. Yokooji, Y., Tomita, H., Atomi, H. and Imanaka, T. Pantoate kinase and phosphopantothenate synthetase, two novel enzymes necessary for CoA biosynthesis in the Archaea. J. Biol. Chem. 284 (2009) 28137-28145. [PMID: 19666462]
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—D-lysine ligase
ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + D-lysine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-Nε-D-lysine
Glossary: muramic acid = 2-amino-3-O-[(R)-1-carboxyethyl]-2-deoxy-D-glucose
Other name(s): UDP-MurNAc-L-Ala-D-Glu:D-Lys ligase; D-lysine-adding enzyme
Systematic name: UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate:D-lysine γ-ligase (ADP-forming)
Comments: Involved in the synthesis of cell-wall peptidoglycan. The D-lysine is attached to the peptide chain at the N6 position. The enzyme from Thermotoga maritima also performs the reaction of EC 6.3.2.7, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase.
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References:
1. Boniface, A., Bouhss, A., Mengin-Lecreulx, D. and Blanot, D. The MurE synthetase from Thermotoga maritima is endowed with an unusual D-lysine adding activity. J. Biol. Chem. 281 (2006) 15680-15686. [PMID: 16595662]
Accepted name: N2-citryl-N6-acetyl-N6-hydroxylysine synthase
Reaction: 2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N6-acetyl-N2-citryl-N6-hydroxy-L-lysine
For diagram of reaction click here
Glossary: citryl = 3-hydroxy-3,4-dicarboxybutanoyl
Other name(s): Nα-citryl-Nε-acetyl-Nε-hydroxylysine synthase; iucA (gene name)
Systematic name: citrate:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming)
Comments: Requires Mg2+. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme is believed to form an adenylate intermediate prior to ligation.
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References:
1. Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175-184. [PMID: 4313071]
2. Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096-3101.
3. de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570-578. [PMID: 2935523]
4. Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437-443.
5. Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601-611. [PMID: 15719346]
6. Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530-6541. [PMID: 19865642]
Accepted name: aerobactin synthase
Reaction: ATP + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine + N6-acetyl-N6-hydroxy-L-lysine = AMP + diphosphate + aerobactin
For diagram of reaction click here
Other name(s): iucC (gene name)
Systematic name: N2-citryl-N6-acetyl-N6-hydroxy-L-lysine:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming)
Comments: Requires Mg2+. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C enzymes are responsible for the formation of amide or ester bonds between a variety of substrates and a prochiral carboxyl group of a citrate molecule that is already linked to a different moiety at its other prochiral carboxyl group. The enzyme is believed to form an adenylate intermediate prior to ligation.
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References:
1. Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175-184. [PMID: 4313071]
2. Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096-3101.
3. Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437-443.
4. de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570-578. [PMID: 2935523]
5. de Lorenzo, V. and Neilands, J.B. Characterization of iucA and iucC genes of the aerobactin system of plasmid ColV-K30 in Escherichia coli. J. Bacteriol. 167 (1986) 350-355. [PMID: 3087960]
6. Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601-611. [PMID: 15719346]
7. Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530-6541. [PMID: 19865642]
Accepted name: cyclopeptine synthase
Reaction: 2 ATP + S-adenosyl-L-methionine + anthranilate + L-phenylalanine = cyclopeptine + 2 AMP + 2 diphosphate + S-adenosyl-L-homocysteine
For diagram of reaction click here.
Glossary: cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
Systematic name: S-adenosyl-L-methionine:anthranilate:L-phenylalanine ligase (cyclopeptine forming)
Comments: Cyclopeptine synthase is the key enzyme of benzodiazepine alkaloid biosynthesis in several fungi species. The enzyme is a non-ribosomal peptide synthase. It is also active with O-methyl-
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References:
1. Lerbs, W. and Luckner, M. Cyclopeptine synthetase activity in surface cultures of Penicillium cyclopium. J. Basic Microbiol. 25 (1985) 387-391. [PMID: 2995633]
2. Gerlach, M, Schwelle, N., Lerbs, W. and Luckner, M. Enzymatic synthesis of cyclopeptine intermediates in Penicillium cyclopium. Phytochemistry 24 (1985) 1935-1939.
3. Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880-12884. [PMID: 25251934]
Accepted name: N-acetylaspartylglutamate synthase
Reaction: ATP + N-acetyl-L-aspartate + L-glutamate = ADP + phosphate + N-acetyl-L-aspartyl-L-glutamate
Other name(s): N-acetylaspartylglutamate synthetase; NAAG synthetase; NAAGS; RIMKLA (gene name) (ambiguous); RIMKLB (gene name) (ambiguous)
Systematic name: N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamate-forming)
Comments: The enzyme, found in animals, produces the neurotransmitter N-acetyl-L-aspartyl-L-glutamate. One isoform also has the activity of EC 6.3.1.17, β-citrylglutamate synthase [2], while another isoform has the activity of EC 6.3.2.42, N-acetylaspartylglutamylglutamate synthase [3].
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References:
1. Becker, I., Lodder, J., Gieselmann, V. and Eckhardt, M. Molecular characterization of N-acetylaspartylglutamate synthetase. J. Biol. Chem. 285 (2010) 29156-29164. [PMID: 20643647]
2. Collard, F., Stroobant, V., Lamosa, P., Kapanda, C.N., Lambert, D.M., Muccioli, G.G., Poupaert, J.H., Opperdoes, F. and Van Schaftingen, E. Molecular identification of N-acetylaspartylglutamate synthase and β-citrylglutamate synthase. J. Biol. Chem. 285 (2010) 29826-29833. [PMID: 20657015]
3. Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693-16706. [PMID: 21454531]
Accepted name: N-acetylaspartylglutamylglutamate synthase
Reaction: 2 ATP + N-acetyl-L-aspartate + 2 L-glutamate = 2 ADP + 2 phosphate + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate
Other name(s): N-acetylaspartylglutamylglutamate synthetase; NAAG(2) synthase; NAAG synthetase II; NAAGS-II; RIMKLA (gene name) (ambiguous)
Systematic name: N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamyl-L-glutamate-forming)
Comments: The enzyme, found in mammals, also has the activity of EC 6.3.2.41, N-acetylaspartylglutamate synthase.
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References:
1. Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693-16706. [PMID: 21454531]
Accepted name: [amino group carrier protein]—L-2-aminoadipate ligase
Reaction: ATP + an [amino group carrier protein]-C-terminal-L-glutamate + L-2-aminoadipate = ADP + phosphate + an [amino group carrier protein]-C-terminal-N-(1,5-dicarboxypentan-1-yl)-L-glutamine
Other name(s): α-aminoadipate-lysW ligase lysX (gene name); LysX (ambiguous); AAA—LysW ligase; [lysine-biosynthesis-protein LysW]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming); [lysine-biosynthesis-protein LysW]—L-2-aminoadipate ligase
Systematic name: [amino group carrier protein]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming)
Comments: The enzymes from the thermophilic bacterium Thermus thermophilus and the thermophilic archaea Sulfolobus acidocaldarius and Sulfolobus tokodaii protect the amino group of L-2-aminoadipate by conjugation to the carrier protein LysW. This reaction is part of the lysine biosynthesis pathway in these organisms.
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References:
1. Vassylyeva, M.N., Sakai, H., Matsuura, T., Sekine, S., Nishiyama, M., Terada, T., Shirouzu, M., Kuramitsu, S., Vassylyev, D.G. and Yokoyama, S. Cloning, expression, purification, crystallization and initial crystallographic analysis of the lysine-biosynthesis LysX protein from Thermus thermophilus HB8. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 1651-1652. [PMID: 12925802]
2. Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673-679. [PMID: 19620981]
3. Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277-283. [PMID: 23434852]
Accepted name: pantoate—β-alanine ligase (ADP-forming)
Reaction: ATP + (R)-pantoate + β-alanine = ADP + phosphate + (R)-pantothenate
For diagram of reaction click here.
Glossary: (R)-pantoate = (2R)-2,4-dihydroxy-3,3-dimethylbutanoate
Other name(s): pantothenate synthetase (ambiguous); pantoate—β-alanine ligase (ambiguous)
Systematic name: (R)-pantoate:β-alanine ligase (ADP-forming)
Comments: The enzyme, characterized from the archaeon Methanosarcina mazei, is involved in the biosynthesis of pantothenate. It is different from EC 6.3.2.1, the AMP-forming pantoate-β-alanine ligase found in bacteria and eukaryota.
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References:
1. Ronconi, S., Jonczyk, R. and Genschel, U. A novel isoform of pantothenate synthetase in the Archaea. FEBS J. 275 (2008) 2754-2764. [PMID: 18422645]
Accepted name: UDP-N-acetylmuramate L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramate + L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate
Glossary: meso-2,6-diaminoheptanedioate = meso-2,6-diaminopimelate
Other name(s): murein peptide ligase; Mpl; yjfG (gene name); UDP-MurNAc:L-Ala-γ-D-Glu-meso-A2pm ligase; UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase
Systematic name: UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase
Comments: The enzyme catalyses the reincorporation into peptidoglycan of the tripeptide L-alanyl-γ-D-glutamyl-2,6-meso-diaminoheptanedioate released during the maturation and constant remodeling of this bacterial cell wall polymer that occur during cell growth and division. The enzyme can also use the tetrapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanine or the pentapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanyl-D-alanine in vivo and in vitro. Requires Mg2+.
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References:
1. Mengin-Lecreulx, D., van Heijenoort, J. and Park, J.T. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan. J. Bacteriol. 178 (1996) 5347-5352. [PMID: 8808921]
2. Herve, M., Boniface, A., Gobec, S., Blanot, D. and Mengin-Lecreulx, D. Biochemical characterization and physiological properties of Escherichia coli UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase. J. Bacteriol. 189 (2007) 3987-3995. [PMID: 17384195]
Accepted name: fumarate—(S)-2,3-diaminopropanoate ligase
Reaction: ATP + fumarate + (S)-2,3-diaminopropanoate = AMP + diphosphate + N3-fumaroyl-(S)-2,3-diaminopropanoate
Glossary: N3-fumaroyl-(S)-2,3-diaminopropanoate = (2E)-4-{[(2S)-2-amino-2-carboxyethyl]amino}-4-oxobut-2-enoate
Other name(s): DdaG
Systematic name: fumarate:(S)-2,3-diaminopropanoate ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Enterobacter agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an (S)-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold.
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References:
1. Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467-10472. [PMID: 19807062]
Accepted name: dapdiamide synthase
Reaction: (1) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-valine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine
Glossary: dapdiamide A = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine
Other name(s): DdaF; dapdiamide A synthase
Systematic name: {[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine:L-valine ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Pantoea agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an (S)-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold.
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References:
1. Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467-10472. [PMID: 19807062]
2. Hollenhorst, M.A., Bumpus, S.B., Matthews, M.L., Bollinger, J.M., Jr., Kelleher, N.L. and Walsh, C.T. The nonribosomal peptide synthetase enzyme DdaD tethers N(β)-fumaramoyl-L-2,3-diaminopropionate for Fe(II)/α-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis. J. Am. Chem. Soc. 132 (2010) 15773-15781. [PMID: 20945916]
Accepted name: L-arginine-specific L-amino acid ligase
Reaction: ATP + L-arginine + an L-amino acid = ADP + phosphate + an L-arginyl-L-amino acid
Other name(s): RizA; L-amino acid ligase RizA
Systematic name: L-arginine:L-amino acid ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, requires Mn2+ for activity. It shows strict substrate specificity toward L-arginine as the first (N-terminal) amino acid of the product. The second amino acid could be any standard protein-building amino acid except for L-proline.
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References:
1. Kino, K., Kotanaka, Y., Arai, T. and Yagasaki, M. A novel L-amino acid ligase from Bacillus subtilis NBRC3134, a microorganism producing peptide-antibiotic rhizocticin. Biosci. Biotechnol. Biochem. 73 (2009) 901-907. [PMID: 19352016]
Accepted name: L-alanine-L-anticapsin ligase
Reaction: ATP + L-alanine + L-anticapsin = ADP + phosphate + bacilysin
For diagram of reaction click here.
Glossary: L-anticapsin = 3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine
Other name(s): BacD; alanine-anticapsin ligase; L-Ala-L-anticapsin ligase; ywfE (gene name)
Systematic name: L-alanine:L-anticapsin ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. The enzyme requires Mg2+ or Mn2+ for activity, and has a broad substrate specificity in vitro [1].
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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]
2. Tsuda, T., Suzuki, T. and Kojima, S. Crystallization and preliminary X-ray diffraction analysis of Bacillus subtilis YwfE, an L-amino-acid ligase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68 (2012) 203-206. [PMID: 22298000]
3. Shomura, Y., Hinokuchi, E., Ikeda, H., Senoo, A., Takahashi, Y., Saito, J., Komori, H., Shibata, N., Yonetani, Y. and Higuchi, Y. Structural and enzymatic characterization of BacD, an L-amino acid dipeptide ligase from Bacillus subtilis. Protein Sci. 21 (2012) 707-716. [PMID: 22407814]
4. Parker, J.B. and Walsh, C.T. Action and timing of BacC and BacD in the late stages of biosynthesis of the dipeptide antibiotic bacilysin. Biochemistry 52 (2013) 889-901. [PMID: 23317005]
Accepted name: tenuazonic acid synthetase
Reaction: ATP + L-isoleucine + acetoacetyl-CoA = AMP + diphosphate + tenuazonic acid + CoA
Glossary: tenuazonic acid = (5S)-3-acetyl-5-[(2S)-butan-2-yl]-4-hydroxy-1,5-dihydro-2H-pyrrol-2-one
Other name(s): TAS1 (gene name)
Systematic name: L-isoleucine:acetoacetyl-CoA ligase (tenuazonic acid-forming)
Comments: This fungal enzyme, isolated from Magnaporthe oryzae, is an non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) hybrid protein that consists of condensation (C), adenylation (A) and peptidyl-carrier protein (PCP) domains in the NRPS portion and a ketosynthase (KS) domain in the PKS portion. ATP is required for activation of isoleucine, which is then condensed with acetoacetyl-CoA. Cyclization and release from the enzyme are catalysed by the KS domain.
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References:
1. Yun, C.S., Motoyama, T. and Osada, H. Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS-PKS hybrid enzyme. Nat Commun 6 (2015) 8758. [PMID: 26503170]
Accepted name: phosphopantothenate—cysteine ligase (ATP)
Reaction: ATP + (R)-4'-phosphopantothenate + L-cysteine = AMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
For diagram of reaction click here.
Other name(s): phosphopantothenoylcysteine synthetase (ambiguous); PPCS (gene name)
Systematic name: (R)-4'-phosphopantothenate:L-cysteine ligase (ATP-utilizing)
Comments: A key enzyme in the production of coenzyme A. The eukaryotic enzyme requires ATP, in contrast to the bacterial enzyme, EC 6.3.2.5, phosphopantothenate—cysteine ligase, which requires CTP.
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References:
1. Daugherty, M. Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. J. Biol. Chem. 277 (2002) 21431-21439. [PMID: 11923312]
2. Manoj, N., Strauss, E., Begley, T.P. and Ealick, S.E. Structure of human phosphopantothenoylcysteine synthetase at 2.3 Å Resolution. Structure 11 (2003) 927-936. [PMID: 12906824]
3. Kupke, T., Hernandez-Acosta, P. and Culianez-Macia, F.A. 4'-phosphopantetheine and coenzyme A biosynthesis in plants. J. Biol. Chem. 278 (2003) 38229-38237. [PMID: 12860978]
Accepted name: jasmonoyl—L-amino acid ligase
Reaction: ATP + jasmonate + an L-amino acid = AMP + diphosphate + a jasmonoyl-L-amino acid
Other name(s): JAR1 (gene name); JAR4 (gene name); JAR6 (gene name); jasmonoyl—L-amino acid synthetase
Systematic name: jasmonate:L-amino acid ligase
Comments: Two jasmonoyl-L-amino acid synthetases have been described from Nicotiana attenuata [3] and one from Arabidopsis thaliana [1]. The N. attenuata enzymes generate jasmonoyl-L-isoleucine, jasmonoyl-L-leucine, and jasmonoyl-L-valine. The enzyme from A. thaliana could catalyse the addition of many different amino acids to jasmonate in vitro [1,4,5]. While the abundant form of jasmonate in plants is (–)-jasmonate, the active form of jasmonoyl-L-isoleucine is (+)-7-iso-jasmonoyl-L-isoleucine.
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1. Staswick, P.E. and Tiryaki, I. The oxylipin signal jasmonic acid is activated by an enzyme that conjugates it to isoleucine in Arabidopsis. Plant Cell 16 (2004) 2117-2127. [PMID: 15258265]
2. Kang, J.H., Wang, L., Giri, A. and Baldwin, I.T. Silencing threonine deaminase and JAR4 in Nicotiana attenuata impairs jasmonic acid-isoleucine-mediated defenses against Manduca sexta. Plant Cell 18 (2006) 3303-3320. [PMID: 17085687]
3. Wang, L., Halitschke, R., Kang, J.H., Berg, A., Harnisch, F. and Baldwin, I.T. Independently silencing two JAR family members impairs levels of trypsin proteinase inhibitors but not nicotine. Planta 226 (2007) 159-167. [PMID: 17273867]
4. Guranowski, A., Miersch, O., Staswick, P.E., Suza, W. and Wasternack, C. Substrate specificity and products of side-reactions catalyzed by jasmonate:amino acid synthetase (JAR1). FEBS Lett. 581 (2007) 815-820. [PMID: 17291501]
5. Suza, W.P. and Staswick, P.E. The role of JAR1 in jasmonoyl-L-isoleucine production during Arabidopsis wound response. Planta 227 (2008) 1221-1232. [PMID: 18247047]
Accepted name: UDP-N-acetylmuramoyl-L-alanine—L-glutamate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanine + L-glutamate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate
Other name(s): murD2 (gene name); UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate synthetase; UDP-MurNAc-L-Ala-L-Glu synthetase
Systematic name: UDP-N-acetylmuramoyl-L-alanine—L-glutamate ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Xanthomonas oryzae, catalyses the ligation of a terminal L-glutamate to UDP-N-acetyl-α-D-muramoyl-L-alanine. The combined activity of this enzyme and EC 5.1.1.23, UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate epimerase, provides an alternative route for incorporating D-glutamate into peptidoglycan, replacing the more common combination of EC 5.1.1.3, glutamate racemase, and EC 6.3.2.9, UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase.
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References:
1. Feng, R., Satoh, Y., Ogasawara, Y., Yoshimura, T. and Dairi, T. A glycopeptidyl-glutamate epimerase for bacterial peptidoglycan biosynthesis. J. Am. Chem. Soc. 139 (2017) 4243-4245. [PMID: 28294606]
Accepted name: L-2,3-diaminopropanoate—citrate ligase
Reaction: ATP + L-2,3-diaminopropanoate + citrate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate
Glossary: staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate
Other name(s): sbnE (gene name); 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate synthtase
Systematic name: L-2,3-diaminopropanoate:citrate ligase (2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate-forming)
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation.
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References:
1. Dale, S.E., Doherty-Kirby, A., Lajoie, G. and Heinrichs, D.E. Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect. Immun. 72 (2004) 29-37. [PMID: 14688077]
2. Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594-608. [PMID: 19775248]
Accepted name: 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate synthase
Reaction: ATP + 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate + L-2,3-diaminopropanoate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate
For diagram of reaction click here
Glossary: staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate
Other name(s): sbnF (gene name)
Systematic name: 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate:L-2,3-diaminopropanoate ligase {2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate-forming}
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C NIS enzymes recognize esterified or amidated derivatives of carboxylic acids. The enzyme likely forms a 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate adenylate intermediate prior to ligation.
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1. Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594-608. [PMID: 19775248]
Accepted name: staphyloferrin B synthase
Reaction: ATP + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate + 2-oxoglutarate = AMP + diphosphate + staphyloferrin B
For diagram of reaction click here
Glossary: staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate
Other name(s): sbnC (gene name)
Systematic name: 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate:2-oxoglutarate ligase (staphyloferrin B-forming)
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type B nonribosomal peptide synthase-independent synthases (NIS). Type B NIS enzymes recognize the δ-acid group of 2-oxoglutarate. The enzyme forms a 2-oxoglutarate adenylate intermediate prior to ligation.
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References:
1. Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594-608. [PMID: 19775248]
Accepted name: staphyloferrin A synthase
Reaction: ATP + N5-[(S)-citryl]-D-ornithine + citrate = AMP + diphosphate + staphyloferrin A
For diagram of reaction click here
Glossary: staphyloferrin A = N2-[(R)-citryl],N5-[(S)-citryl]-D-ornithine
Other name(s): sfnaB (gene name)
Systematic name: N5-[(S)-citryl]-D-ornithine:citrate ligase (staphyloferrin A-forming)
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin A. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation.
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References:
1. Cotton, J.L., Tao, J. and Balibar, C.J. Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48 (2009) 1025-1035. [PMID: 19138128]
Accepted name: D-ornithine—citrate ligase
Reaction: ATP + D-ornithine + citrate = AMP + diphosphate + N5-[(S)-citryl]-D-ornithine
For diagram of reaction, click here
Glossary: staphyloferrin A = N2-[(R)-citryl],N5-[(S)-citryl]-D-ornithine
Other name(s): sfnaD (gene name)
Systematic name: D-ornithine:citrate ligase {3-[(2-aminopentan-5-oylcarbamoyl)methyl]-3-hydroxybutanoate-forming}
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin A. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation.
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References:
1. Cotton, J.L., Tao, J. and Balibar, C.J. Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48 (2009) 1025-1035. [PMID: 19138128]
Accepted name: 3-methyl-D-ornithine—L-lysine ligase
Reaction: ATP + (3R)-3-methyl-D-ornithine + L-lysine = ADP + Pi + N6-[(3R)-3-methyl-D-ornithinyl]-L-lysine
Glossary: L-pyrrolysine = N6-{[(2R,3R)-3-methyl-3,4-dihydro-2H-pyrrol-2-yl]carbonyl}-L-lysine
Other name(s): N6-[(2R,3R)-3-methylornithyl]-L-lysine synthase; 3-methylornithine—L-lysine ligase; pylC (gene name)
Systematic name: (3R)-3-methyl-D-ornithine:L-lysine γ-ligase (ADP-forming)
Comments: The enzyme participates in the biosynthesis of L-pyrrolysine, a naturally occurring, genetically coded amino acid found in some methanogenic archaea and a few bacterial species. L-pyrrolysine is present in several methyltransferases that are involved in methyl transfer from methylated amine compounds to coenzyme M.
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1. Gaston, M.A., Zhang, L., Green-Church, K.B. and Krzycki, J.A. The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine. Nature 471 (2011) 647-650. [PMID: 21455182]
2. Cellitti, S.E., Ou, W., Chiu, H.P., Grunewald, J., Jones, D.H., Hao, X., Fan, Q., Quinn, L.L., Ng, K., Anfora, A.T., Lesley, S.A., Uno, T., Brock, A. and Geierstanger, B.H. D-Ornithine coopts pyrrolysine biosynthesis to make and insert pyrroline-carboxy-lysine. Nat. Chem. Biol. 7 (2011) 528-530. [PMID: 21525873]
3. Quitterer, F., List, A., Beck, P., Bacher, A. and Groll, M. Biosynthesis of the 22nd genetically encoded amino acid pyrrolysine: structure and reaction mechanism of PylC at 1.5A resolution. J. Mol. Biol. 424 (2012) 270-282. [PMID: 22985965]
Accepted name: glutamate—[amino group carrier protein] ligase
Reaction: ATP + L-glutamate + an [amino-group carrier protein]-C-terminal-L-glutamate = ADP + phosphate + an [amino-group carrier protein]-C-terminal-γ-(L-glutamyl)-L-glutamate
Other name(s): argX (gene name)
Systematic name: L-glutamate:an [amino-group carrier protein]-C-terminal-L-glutamate ligase (ADP-forming)
Comments: The enzyme, originally characterized from the archaeon Sulfolobus acidocaldarius, is involved in L-arginine biosynthesis. The enzyme from the archaeon Thermococcus kodakarensis is bifunctional and also catalyses the activity of EC 6.3.2.43, [amino-group carrier protein]—L-2-aminoadipate ligase.
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1. Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277-283. [PMID: 23434852]
2. Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630-21643. [PMID: 27566549]
Accepted name: tubulin-glutamate ligase
Reaction: n ATP + [tubulin]-L-glutamate + n L-glutamate = [tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate (overall reaction)
Other name(s): α-tubulin-glutamate ligase; tubulin polyglutamylase; TTLL1 (ambiguous); TTLL5 (ambiguous); TTLL6 (ambiguous)
Systematic name: [tubulin]-L-glutamate:L-glutamate ligase (ADP-forming)
Comments: The eukaryotic tubulin proteins, which polymerize into microtubules, are highly modified by the addition of side-chains. The polyglutamylation reaction catalysed by this group of enzymes consists of two biochemically distinct steps: initiation and elongation. Initiation comprises the formation of an isopeptide bond with the γ-carboxyl group of the glutamate acceptor site in a glutamate-rich C-terminal region of tubulin, whereas elongation consists of the addition of glutamate residues linked by regular peptide bonds to the γ-linked residue. This entry describes enzymes that act on both α- and β-tubulins.
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1. Regnard, C., Audebert, S., Desbruyeres, Denoulet, P. and Edde, B. Tubulin polyglutamylase: partial purification and enzymatic properties. Biochemistry 37 (1998) 8395-8404. [PMID: 9622491]
2. Regnard, C., Desbruyeres, E., Denoulet, P. and Edde, B. Tubulin polyglutamylase: isozymic variants and regulation during the cell cycle in HeLa cells. J. Cell Sci. 112 (1999) 4281-4289. [PMID: 10564646]
3. Westermann, S., Plessmann, U. and Weber, K. Synthetic peptides identify the minimal substrate requirements of tubulin polyglutamylase in side chain elongation. FEBS Lett. 459 (1999) 90-94. [PMID: 10508923]
4. Janke, C., Rogowski, K., Wloga, D., Regnard, C., Kajava, A.V., Strub, J.M., Temurak, N., van Dijk, J., Boucher, D., van Dorsselaer, A., Suryavanshi, S., Gaertig, J. and Edde, B. Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Science 308 (2005) 1758-1762. [PMID: 15890843]
5. van Dijk, J., Rogowski, K., Miro, J., Lacroix, B., Edde, B. and Janke, C. A targeted multienzyme mechanism for selective microtubule polyglutamylation. Mol. Cell 26 (2007) 437-448. [PMID: 17499049]
6. Wloga, D., Rogowski, K., Sharma, N., Van Dijk, J., Janke, C., Edde, B., Bre, M.H., Levilliers, N., Redeker, V., Duan, J., Gorovsky, M.A., Jerka-Dziadosz, M. and Gaertig, J. Glutamylation on α-tubulin is not essential but affects the assembly and functions of a subset of microtubules in Tetrahymena thermophila, Eukaryot Cell 7 (2008) 1362-1372. [PMID: 18586949]
7. van Dijk, J., Miro, J., Strub, J.M., Lacroix, B., van Dorsselaer, A., Edde, B. and Janke, C. Polyglutamylation is a post-translational modification with a broad range of substrates. J. Biol. Chem. 283 (2008) 3915-3922. [PMID: 18045879]
Accepted name: β-tubulin-glutamate ligase
Reaction: n ATP + [β-tubulin]-L-glutamate + n L-glutamate = [β-tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate (overall reaction)
Other name(s): β-tubulin polyglutamylase; TTLL4 (ambiguous); TTLL7 (ambiguous)
Systematic name: [β-tubulin]-L-glutamate:L-glutamate ligase (ADP-forming)
Comments: The eukaryotic tubulin proteins, which polymerize into microtubules, are highly modified by the addition of side-chains. The polyglutamylation reaction catalysed by this group of enzymes consists of two biochemically distinct steps: initiation and elongation. Initiation comprises the formation of an isopeptide bond with the γ-carboxyl group of the glutamate acceptor site, whereas elongation consists of the addition of glutamate residues linked by regular peptide bonds to the γ-linked residue. This entry describes enzymes that act on β-tubulins and other proteins with glutamate-rich regions but not on α-tubulins.
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References:
1. Regnard, C., Audebert, S., Desbruyeres, Denoulet, P. and Edde, B. Tubulin polyglutamylase: partial purification and enzymatic properties. Biochemistry 37 (1998) 8395-8404. [PMID: 9622491]
2. Regnard, C., Desbruyeres, E., Denoulet, P. and Edde, B. Tubulin polyglutamylase: isozymic variants and regulation during the cell cycle in HeLa cells. J. Cell Sci. 112 (1999) 4281-4289. [PMID: 10564646]
3. Ikegami, K., Mukai, M., Tsuchida, J., Heier, R.L., Macgregor, G.R. and Setou, M. TTLL7 is a mammalian β-tubulin polyglutamylase required for growth of MAP2-positive neurites. J. Biol. Chem. 281 (2006) 30707-30716. [PMID: 16901895]
4. van Dijk, J., Miro, J., Strub, J.M., Lacroix, B., van Dorsselaer, A., Edde, B. and Janke, C. Polyglutamylation is a post-translational modification with a broad range of substrates. J. Biol. Chem. 283 (2008) 3915-3922. [PMID: 18045879]
Accepted name: putrebactin synthase
Reaction: 2 ATP + 2 N1-hydroxy-N1-succinylputrescine = 2 AMP + 2 diphosphate + putrebactin (overall reaction)
For diagram of reaction click here
Glossary: putrebactin = 1,11-dihydroxy-1,6,11,16-tetraazacycloicosane-2,5,12,15-tetrone
Other name(s): pubC (gene name)
Systematic name: N1-hydroxy-N1-succinylputrescine:N1-hydroxy-N1-succinylputrescine ligase
Comments: Requires Mg2+. The enzyme, characterized from the bacteria Shewanella spp. MR-4 and MR-7, catalyse the last step in the biosynthesis of the siderophore putrebactin. The enzyme catalyses the reaction in two steps - concatenation of two molecules of N1-hydroxy-N1-succinylputrescine, followed by cyclization.
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1. Kadi, N., Arbache, S., Song, L., Oves-Costales, D. and Challis, G.L. Identification of a gene cluster that directs putrebactin biosynthesis in Shewanella species: PubC catalyzes cyclodimerization of N-hydroxy-N-succinylputrescine. J. Am. Chem. Soc. 130 (2008) 10458-10459. [PMID: 18630910]
Accepted name: bisucaberin synthase
Reaction: 2 ATP + 2 N1-hydroxy-N1-succinylcadaverine = 2 AMP + 2 diphosphate + bisucaberin (overall reaction)
Glossary: bisucaberin B = pre-bisucaberin = 3-[(5-{3-[(5-aminopentyl)(hydroxy)carbamoyl]propanamido}pentyl)(hydroxy)carbamoyl]propanoate
Other name(s): pubC (gene name); BibC C-terminal domain
Systematic name: N1-hydroxy-N1-succinylcadaverine:N1-hydroxy-N1-succinylcadaverine ligase
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Aliivibrio salmonicida, catalyses the last step in the biosynthesis of the siderophore bisucaberin. The enzyme catalyses the reaction in two steps - concatenation of two molecules of N1-hydroxy-N1-succinylcadaverine, followed by cyclization.
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1. Kadi, N., Song, L. and Challis, G.L. Bisucaberin biosynthesis: an adenylating domain of the BibC multi-enzyme catalyzes cyclodimerization of N-hydroxy-N-succinylcadaverine. Chem. Commun. (Camb.) (2008) 5119-5121. [PMID: 18956041]
Accepted name: UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose:2-oxoglutarate ligase
Reaction: ATP + UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose + 2-oxoglutarate = ADP + phosphate + UDP-yelosamine
Glossary: UDP-yelosamine = UDP-N-acetyl-D-fucosamine-4N-(2)-oxoglutarate = UDP-D-FucNAc-4N-(2)-oxoglutarate
Other name(s): Pyl
Systematic name: UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose:2-oxoglutarate ligase (ADP-forming)
Comments: The enzyme, discovered in the bacterium Bacillus cereus ATCC 14579, produces the unusual nucleotide sugar UDP-yelosamine, which is incorporated into the capsular polysaccharide of this organism.
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1. Hwang, S., Li, Z., Bar-Peled, Y., Aronov, A., Ericson, J. and Bar-Peled, M. The biosynthesis of UDP-D-FucNAc-4N-2-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars. J. Biol. Chem. 289 (2014) 35620-35632. [PMID: 25368324]
(R)-pantothenate = 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate
L-2,3-diaminopropanoate = (S)-2,3-diaminopropanoate
(2) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-isoleucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine
(3) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-leucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine
(4) ATP + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanine + L-valine = ADP + phosphate + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanyl-L-valine
dapdiamide B = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine
dapdiamide C = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine
bacilysin = L-alanyl-3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine
citryl = 3-hydroxy-3,4-dicarboxybutanoyl
(1a) ATP + [tubulin]-L-glutamate + L-glutamate = [tubulin]-(γ-L-glutamyl)-L-glutamate + ADP + phosphate
(1b) ATP + [tubulin]-(γ-L-glutamyl)-L-glutamate + L-glutamate = [tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + ADP + phosphate
(1c) n ATP + [tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + n L-glutamate = [tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate
(1a) ATP + [β-tubulin]-L-glutamate + L-glutamate = [β-tubulin]-(γ-L-glutamyl)-L-glutamate + ADP + phosphate
(1b) ATP + [β-tubulin]-(γ-L-glutamyl)-L-glutamate + L-glutamate = [β-tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + ADP + phosphate
(1c) n ATP + [β-tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + n L-glutamate = [β-tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate
(1a) ATP + 2 N1-hydroxy-N1-succinylputrescine = AMP + diphosphate + pre-putrebactin
(1b) ATP + pre-putrebactin = AMP + diphosphate + putrebactin
pre-putrebactin = 4-{[4-({4-[(4-aminobutyl)(hydroxy)amino]-4-oxobutanoyl}amino)butyl](hydroxy)amino}-4-oxobutanoate
(1a) ATP + 2 N1-hydroxy-N1-succinylcadaverine = AMP + diphosphate + bisucaberin B
(1b) ATP + bisucaberin B = AMP + diphosphate + bisucaberin
bisucaberin = 1,12-dihydroxy-1,6,12,17-tetrazacyclodocosane-2,5,13,16-tetrone
Continued with EC 6.3.3 to EC 6.3.5
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