Enzyme Nomenclature

Continued from EC 6.3.1 and EC 6.3.2

EC 6.3.3 to EC 6.3.5

Sections

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


EC 6.3.3 Cyclo-Ligases

Contents

EC 6.3.3.1 phosphoribosylformylglycinamidine cyclo-ligase
EC 6.3.3.2 5-formyltetrahydrofolate cyclo-ligase
EC 6.3.3.3 dethiobiotin synthase
EC 6.3.3.4 (carboxyethyl)arginine β-lactam-synthase
EC 6.3.3.5 O-ureido-D-serine cyclo-ligase
EC 6.3.3.6 carbapenam-3-carboxylate synthase
EC 6.3.3.7 Ni-sirohydrochlorin a,c-diamide reductive cyclase


Entries

EC 6.3.3.1

Accepted name: phosphoribosylformylglycinamidine cyclo-ligase

Reaction: ATP + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole

For reaction pathway click here.

Other name(s): phosphoribosylaminoimidazole synthetase; AIR synthetase; 5'-aminoimidazole ribonucleotide synthetase

Systematic name: 2-(formamido)-N1-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-53-4

References:

1. Levenberg, B. and Buchanan, J.M. Properties of the purines. XII. Structure, enzymatic synthesis, and metabolism of 5-aminoimidazole ribotide. J. Biol. Chem. 224 (1957) 1005-1018.

2. Levenberg, B. and Buchanan, J.M. Properties of the purines. XIII. Structure, enzymatic synthesis, and metabolism of (α-N-formyl)-glycinamidine ribotide. J. Biol. Chem. 224 (1957) 1018-1027.

[EC 6.3.3.1 created 1961, modified 2000]

EC 6.3.3.2

Accepted name: 5-formyltetrahydrofolate cyclo-ligase

Reaction: ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate

For diagram of reaction click here (another example).

Other name(s): 5,10-methenyltetrahydrofolate synthetase; formyltetrahydrofolic cyclodehydrase; 5-formyltetrahydrofolate cyclodehydrase

Systematic name: 5-formyltetrahydrofolate cyclo-ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-64-2

References:

1. Greenberg, D.M., Wynston, L.K. and Nagabhushanan, A. Further studies on N5-formyltetrahydrofolic acid cyclodehydrase. Biochemistry 4 (1965) 1872-1878.

[EC 6.3.3.2 created 1972]

EC 6.3.3.3

Accepted name: dethiobiotin synthase

Reaction: ATP + 7,8-diaminononanoate + CO2 = ADP + phosphate + dethiobiotin

Other name(s): desthiobiotin synthase

Systematic name: 7,8-diaminononanoate:carbon-dioxide cyclo-ligase (ADP-forming)

Comments: CTP has half the activity of ATP.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37259-75-9

References:

1. Krell, K. and Eisenberg, M.A. The purification and properties of dethiobiotin synthetase. J. Biol. Chem. 245 (1970) 6558-6566. [PMID: 4921568]

2. Yang, H.-C., Tani, Y. and Ogata, K. Synthesis of biotin vitamers from biotin diaminocarboxylic acid or 7,8-diaminopelargonic acid by a purified enzyme of Pseudomonas graveolens. Agric. Biol. Chem. 34 (1970) 1748-1750.

[EC 6.3.3.3 created 1976]

EC 6.3.3.4

Accepted name: (carboxyethyl)arginine β-lactam-synthase

Reaction: ATP + L-N2-(2-carboxyethyl)arginine = AMP + diphosphate + deoxyamidinoproclavaminate

For diagram click here.

Systematic name: L-N2-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming)

Comments: Forms part of the pathway for the biosythesis of the β-lactamase inhibitor clavulanate in Streptomyces clavuligerus. It has been proposed [3] that L-N2-(2-carboxyethyl)arginine is first converted into an acyl-AMP by reaction with ATP and loss of diphosphate, and that the β-lactam ring is then formed by the intramolecular attack of the β-nitrogen on the activated carboxy group.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A. and Solomon, E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123 (2001) 7388-7398.

2. Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6 (2002) 583-589. [PMID: 12413541]

3. Bachmann, B.O., Li, R. and Townsend, C.A. β-Lactam synthetase: a new biosynthetic enzyme. Proc. Natl. Acad. Sci. USA 95 (1998) 9082-9086. [PMID: 9689037]

[EC 6.3.3.4 created 2003]

EC 6.3.3.5

Accepted name: O-ureido-D-serine cyclo-ligase

Reaction: O-ureido-D-serine + ATP + H2O = D-cycloserine + CO2 + 3 + ADP + phosphate

Glossary: O-ureido-D-serine = (2R)-2-amino-3-[(carbamoylamino)oxy]propanoate

Other name(s): dcsG (gene name)

Systematic name: O-ureido-D-serine cyclo-ligase (D-cycloserine-forming)

Comments: The enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Kumagai, T., Koyama, Y., Oda, K., Noda, M., Matoba, Y. and Sugiyama, M. Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae. Antimicrob. Agents Chemother. 54 (2010) 1132-1139. [PMID: 20086163]

2. Uda, N., Matoba, Y., Kumagai, T., Oda, K., Noda, M. and Sugiyama, M. Establishment of an in vitro D-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway. Antimicrob. Agents Chemother. 57 (2013) 2603-2612. [PMID: 23529730]

[EC 6.3.3.5 created 2013]

EC 6.3.3.6

Accepted name: carbapenam-3-carboxylate synthase

Reaction: ATP + (2S,5S)-5-carboxymethylproline = AMP + diphosphate + (3S,5S)-carbapenam 3-carboxylate

Other name(s): CarA (ambiguous); CPS (ambiguous); carbapenam-3-carboxylate ligase

Systematic name: (2S,5S)-5-carboxymethylproline cyclo-ligase (AMP-forming)

Comments: The enzyme is involved in the biosynthesis of the carbapenem β-lactam antibiotic (5R)-carbapen-2-em-3-carboxylate in the bacterium Pectobacterium carotovorum.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Gerratana, B., Stapon, A. and Townsend, C.A. Inhibition and alternate substrate studies on the mechanism of carbapenam synthetase from Erwinia carotovora. Biochemistry 42 (2003) 7836-7847. [PMID: 12820893]

2. Miller, M.T., Gerratana, B., Stapon, A., Townsend, C.A. and Rosenzweig, A.C. Crystal structure of carbapenam synthetase (CarA). J. Biol. Chem. 278 (2003) 40996-41002. [PMID: 12890666]

3. Raber, M.L., Arnett, S.O. and Townsend, C.A. A conserved tyrosyl-glutamyl catalytic dyad in evolutionarily linked enzymes: carbapenam synthetase and β-lactam synthetase. Biochemistry 48 (2009) 4959-4971. [PMID: 19371088]

4. Arnett, S.O., Gerratana, B. and Townsend, C.A. Rate-limiting steps and role of active site Lys443 in the mechanism of carbapenam synthetase. Biochemistry 46 (2007) 9337-9345. [PMID: 17658887]

[EC 6.3.3.6 created 2013 as EC 6.3.1.16, transferred 2013 to EC 6.3.3.6]

EC 6.3.3.7

Accepted name: Ni-sirohydrochlorin a,c-diamide reductive cyclase

Reaction: ATP + Ni-sirohydrochlorin a,c-diamide + 3 reduced electron acceptor + H2O = ADP + phosphate + 15,173-seco-F430-173-acid + 3 electron acceptor

For diagram of reaction click here.

Other name(s): cfbC (gene name); cfbD (gene name)

Systematic name: Ni-sirohydrochlorin a,c-diamide reductive cyclo-ligase (ADP-forming)

Comments: The enzyme, studied from the methanogenic archaeon Methanosarcina acetivorans, participates in the biosynthesis of the nickel-containing tetrapyrrole cofactor coenzyme F430, which is required by EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Pfaltz, A., Kobelt, A., Huster, R. and Thauer, R.K. Biosynthesis of coenzyme F430 in methanogenic bacteria. Identification of 15,173-seco-F430-173-acid as an intermediate. Eur. J. Biochem. 170 (1987) 459-467. [PMID: 3691535]

2. Zheng, K., Ngo, P.D., Owens, V.L., Yang, X.P. and Mansoorabadi, S.O. The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354 (2016) 339-342. [PMID: 27846569]

[EC 6.3.3.7 created 2017]


EC 6.3.4 Other Carbon—Nitrogen Ligases

Contents

EC 6.3.4.1 transferred now included in EC 6.3.5.2
EC 6.3.4.2 CTP synthase (glutamine hydrolysing)
EC 6.3.4.3 formate—tetrahydrofolate ligase
EC 6.3.4.4 adenylosuccinate synthase
EC 6.3.4.5 argininosuccinate synthase
EC 6.3.4.6 urea carboxylase
EC 6.3.4.7 ribose-5-phosphate—ammonia ligase
EC 6.3.4.8 imidazoleacetate—phosphoribosyldiphosphate ligase
EC 6.3.4.9 biotin—[methylmalonyl-CoA-carboxytransferase] ligase
EC 6.3.4.10 biotin—[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase
EC 6.3.4.11 biotin—[methylcrotonoyl-CoA-carboxylase] ligase
EC 6.3.4.12 glutamate—methylamine ligase
EC 6.3.4.13 phosphoribosylamine—glycine ligase
EC 6.3.4.14 biotin carboxylase
EC 6.3.4.15 biotin—[biotin carboxyl-carrier protein] ligase
EC 6.3.4.16 carbamoyl-phosphate synthase (ammonia)
EC 6.3.4.17 formate—dihydrofolate ligase
EC 6.3.4.18 5-(carboxyamino)imidazole ribonucleotide synthase
EC 6.3.4.19 tRNAIle-lysidine synthetase
EC 6.3.4.20 7-cyano-7-deazaguanine synthase
EC 6.3.4.21 nicotinate phosphoribosyltransferase
EC 6.3.4.22 tRNAIle2-agmatinylcytidine synthase
EC 6.3.4.23 formate—phosphoribosylaminoimidazolecarboxamide ligase
EC 6.3.4.24 tyramine—L-glutamate ligase


Entries

[EC 6.3.4.1 Transferred entry: GMP synthase. Now included in EC 6.3.5.2, GMP synthase (glutamine-hydrolysing). (EC 6.3.4.1 created 1961, deleted 2013)]

EC 6.3.4.2

Accepted name: CTP synthase (glutamine hydrolysing)

Reaction: ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + UTP + NH3 = ADP + phosphate + CTP

Other name(s): UTP—ammonia ligase; cytidine triphosphate synthetase; uridine triphosphate aminase; cytidine 5'-triphosphate synthetase; CTPS (gene name); pyrG (gene name)

Systematic name: UTP:L-glutamine amido-ligase (ADP-forming)

Comments: The enzyme contains three functionally distinct sites: an allosteric GTP-binding site, a glutaminase site where glutamine hydrolysis occurs (cf. EC 3.5.1.2, glutaminase), and the active site where CTP synthesis takes place. The reaction proceeds via phosphorylation of UTP by ATP to give an activated intermediate 4-phosphoryl UTP and ADP [4,5]. Ammonia then reacts with this intermediate generating CTP and a phosphate. The enzyme can also use ammonia from the surrounding solution [3,6].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-56-7

References:

1. Lieberman, I. Enzymatic amination of uridine triphosphate to cytidine triphosphate. J. Biol. Chem. 222 (1956) 765-775. [PMID: 13367044]

2. Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342.

3. Levitzki, A. and Koshland, D.E., Jr. Ligand-induced dimer-to-tetramer transformation in cytosine triphosphate synthetase. Biochemistry 11 (1972) 247-253. [PMID: 4550560]

4. von der Saal, W., Anderson, P.M. and Villafranca, J.J. Mechanistic investigations of Escherichia coli cytidine-5'-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments. J. Biol. Chem. 260 (1985) 14993-14997. [PMID: 2933396]

5. Lewis, D.A. and Villafranca, J.J. Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods. Biochemistry 28 (1989) 8454-8459. [PMID: 2532543]

6. Wadskov-Hansen, S.L., Willemoes, M., Martinussen, J., Hammer, K., Neuhard, J. and Larsen, S. Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase. J. Biol. Chem. 276 (2001) 38002-38009. [PMID: 11500486]

[EC 6.3.4.2 created 1961, modified 2013]

EC 6.3.4.3

Accepted name: formate—tetrahydrofolate ligase

Reaction: ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate

For diagram of reaction click here (another example).

Other name(s): formyltetrahydrofolate synthetase; 10-formyltetrahydrofolate synthetase; tetrahydrofolic formylase; tetrahydrofolate formylase

Systematic name: formate:tetrahydrofolate ligase (ADP-forming)

Comments: In eukaryotes occurs as a trifunctional enzyme also having methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9023-66-9

References:

1. Jaenicke, L. and Brode, E. Untersuchungen über Einkohlenstoffkörper. I. Die Tetrahydrofolatformylase aus Taubenleber. Rinigung und Mechanismus. Biochem. Z. 334 (1961) 108-132.

2. Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342 only.

3. Rabinowitz, J.C. and Pricer, W.E. Formyltetrahydrofolate synthetase. I. Isolation and crystallization of the enzyme. J. Biol. Chem. 237 (1962) 2898-2902.

4. Whiteley, H.R., Osborn, M.J. and Huennekens, F.M. Purification and properties of the formate-activating enzyme from Micrococcus aerogenes. J. Biol. Chem. 234 (1959) 1538-1543.

[EC 6.3.4.3 created 1961]

EC 6.3.4.4

Accepted name: adenylosuccinate synthase

Reaction: GTP + IMP + L-aspartate = GDP + phosphate + N6-(1,2-dicarboxyethyl)-AMP

For diagram click here.

Other name(s): IMP—aspartate ligase; adenylosuccinate synthetase; succinoadenylic kinosynthetase; succino-AMP synthetase

Systematic name: IMP:L-aspartate ligase (GDP-forming)

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9023-57-8

References:

1. Davey, C.L. Synthesis of adenylosuccinic acid in preparations of mammalian skeletal muscle. Nature 183 (1959) 995-996.

2. Lieberman, I. Enzymatic synthesis of adenosine-5'-phosphate from inosine-5'-phosphate. J. Biol. Chem. 223 (1956) 327-339.

3. Yefimochkina, E.F. and Braunstein, A.E. The amination of inosinic acid to adenylic acid in muscle extracts. Arch. Biochem. Biophys. 83 (1959) 350-352.

[EC 6.3.4.4 created 1961]

EC 6.3.4.5

Accepted name: argininosuccinate synthase

Reaction: ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nω-L-arginino)succinate

For diagram click here.

Other name(s): citrulline—aspartate ligase; argininosuccinate synthetase; arginine succinate synthetase; argininosuccinic acid synthetase; arginosuccinate synthetase

Systematic name: L-citrulline:L-aspartate ligase (AMP-forming)

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9023-58-9

References:

1. Ratner, S. Urea synthesis and metabolism of arginine and citrulline. Adv. Enzymol. Relat. Subj. Biochem. 15 (1954) 319-387.

2. Schuegraf, A., Ratner, S. and Warner, R.C. Free energy changes of the argininosuccinate synthetase reaction and of the hydrolysis of the inner pyrophosphate bond of adenosine triphosphate. J. Biol. Chem. 235 (1960) 3597-3602.

[EC 6.3.4.5 created 1961]

EC 6.3.4.6

Accepted name: urea carboxylase

Reaction: ATP + urea + HCO3- = ADP + phosphate + urea-1-carboxylate

Glossary: allophanate = urea-1-carboxylate

Other name(s): urease (ATP-hydrolysing); urea carboxylase (hydrolysing); ATP—urea amidolyase; urea amido-lyase; UALase; UCA

Systematic name: urea:carbon-dioxide ligase (ADP-forming)

Comments: A biotinyl-protein. The yeast enzyme (but not that from green algae) also catalyses the reaction of EC 3.5.1.54 allophanate hydrolase, thus bringing about the hydrolysis of urea to CO2 and NH3. Previously also listed as EC 3.5.1.45. The enzyme from the prokaryotic bacterium Oleomonas sagaranensis can also use acetamide and formamide as substrates [4].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9058-98-4

References:

1. Roon, R.J. and Levenberg, B. ATP-Urea amidolyase (ADP) (Candida utilis). Methods Enzymol. 17A (1970) 317-324.

2. Roon, R.J. and Levenberg, B. Urea amidolyase. I. Properties of the enzyme from Candida utilis. J. Biol. Chem. 247 (1972) 4107-4113. [PMID: 4556303]

3. Sumrada, R.A. and Cooper, T.G. Urea carboxylase and allophanate hydrolase are components of a multifunctional protein in yeast. J. Biol. Chem. 257 (1982) 9119-9127. [PMID: 6124544]

4. Kanamori, T., Kanou, N., Atomi, H. and Imanaka, T. Enzymatic characterization of a prokaryotic urea carboxylase. J. Bacteriol. 186 (2004) 2532-2539. [PMID: 15090492]

[EC 6.3.4.6 created 1972, modified 1986 (EC 3.5.1.45 created 1978, incorporated 1986)]

EC 6.3.4.7

Accepted name: ribose-5-phosphate—ammonia ligase

Reaction: ATP + ribose 5-phosphate + NH3 = ADP + phosphate + 5-phosphoribosylamine

For diagram of reaction click here.

Other name(s): 5-phosphoribosylamine synthetase; ribose 5-phosphate aminotransferase; ammonia-ribose 5-phosphate aminotransferase

Systematic name: ribose-5-phosphate:ammonia ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9082-52-4

References:

1. Reem, G.H. Enzymatic synthesis of 5'-phosphoribosylamine from ribose 5-phosphate and ammonia, an alternate first step in purine biosynthesis. J. Biol. Chem. 243 (1968) 5695-5701. [PMID: 5699059]

[EC 6.3.4.7 created 1972]

EC 6.3.4.8

Accepted name: imidazoleacetate—phosphoribosyldiphosphate ligase

Reaction: ATP + imidazole-4-acetate + 5-phosphoribosyl diphosphate + H2O = ADP + phosphate + 1-(5-phosphoribosyl)imidazole-4-acetate + diphosphate

Other name(s): 5-phosphoribosylimidazoleacetate synthetase

Systematic name: imidazoleacetate:5-phosphoribosyl-diphosphate ligase (ADP- and diphosphate-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-65-3

References:

1. Crowley, G.M. The enzymatic synthesis of 5'-phosphoribosylimidazoleacetic acid. J. Biol. Chem. 239 (1964) 2593-2601.

[EC 6.3.4.8 created 1972]

EC 6.3.4.9

Accepted name: biotin—[methylmalonyl-CoA-carboxytransferase] ligase

Reaction: ATP + biotin + apo-[methylmalonyl-CoA:pyruvate carboxytransferase] = AMP + diphosphate + [methylmalonyl-CoA:pyruvate carboxytransferase]

Other name(s): biotin-[methylmalonyl-CoA-carboxyltransferase] synthetase; biotin-methylmalonyl coenzyme A carboxyltransferase synthetase; biotin-transcarboxylase synthetase; methylmalonyl coenzyme A holotranscarboxylase synthetase; biotin—[methylmalonyl-CoA-carboxyltransferase] ligase; biotin:apo[methylmalonyl-CoA:pyruvate carboxyltransferase] ligase (AMP-forming)

Systematic name: biotin:apo[methylmalonyl-CoA:pyruvate carboxytransferase] ligase (AMP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-66-4

References:

1. Lane, M.D., Young, D.L. and Lynen, F. The enzymatic synthesis of holotranscarboxylase from apotranscarboxylase and (+)-biotin. I. Purification of the apoenzyme and synthetase; characteristics of the reaction. J. Biol. Chem. 239 (1964) 2858-2864.

[EC 6.3.4.9 created 1972]

EC 6.3.4.10

Accepted name: biotin—[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase

Reaction: ATP + biotin + apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [propionyl-CoA:carbon-dioxide ligase (ADP-forming)]

Other name(s): biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] synthetase; biotin-propionyl coenzyme A carboxylase synthetase; propionyl coenzyme A holocarboxylase synthetase

Systematic name: biotin:apo-[propanoyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-67-5

References:

1. Siegel, L., Foote, J.L. and Coon, M.J. The enzymatic synthesis of propionyl coenzyme A holocarboxylase from d-biotinyl 5'-adenylate and the apocarboxylase. J. Biol. Chem. 240 (1965) 1025-1031.

[EC 6.3.4.10 created 1972]

EC 6.3.4.11

Accepted name: biotin—[methylcrotonoyl-CoA-carboxylase] ligase

Reaction: ATP + biotin + apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)]

Other name(s): biotin-[methylcrotonoyl-CoA-carboxylase] synthetase; biotin-β-methylcrotonyl coenzyme A carboxylase synthetase; β-methylcrotonyl coenzyme A holocarboxylase synthetase; holocarboxylase-synthetase

Systematic name: biotin:apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-68-6

References:

1. Höpner, T. and Knappe, J. Einbau von Biotin in β-methylcrotonyl-CoA-carboxylase urch Holocarboxylase-synthetase. Biochem. Z. 342 (1965) 190-206. [PMID: 5867144]

[EC 6.3.4.11 created 1972]

EC 6.3.4.12

Accepted name: glutamate—methylamine ligase

Reaction: ATP + L-glutamate + methylamine = ADP + phosphate + N5-methyl-L-glutamine

Other name(s): γ-glutamylmethylamide synthetase

Systematic name: L-glutamate:methylamine ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 37318-69-7

References:

1. Kung, H.-F. and Wagner, C. γ-Glutamylmethylamide. A new intermediate in the metabolism of methylamine. J. Biol. Chem. 244 (1969) 4136-4140. [PMID: 5800436]

[EC 6.3.4.12 created 1972]

EC 6.3.4.13

Accepted name: phosphoribosylamine—glycine ligase

Reaction: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N1-(5-phospho-D-ribosyl)glycinamide

For reaction pathway click here.

Other name(s): phosphoribosylglycinamide synthetase; glycinamide ribonucleotide synthetase; phosphoribosylglycineamide synthetase; glycineamide ribonucleotide synthetase; 2-amino-N-ribosylacetamide 5'-phosphate kinosynthase; 5'-phosphoribosylglycinamide synthetase; GAR

Systematic name: 5-phospho-D-ribosylamine:glycine ligase (ADP-forming)

Comments: Formerly EC 6.3.1.3.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9032-01-3

References:

1. Goldthwait, D.A., Peabody, R.A. and Greenberg, G.R. On the mechanism of synthesis of glycinamide ribotide and its formyl derivative. J. Biol. Chem. 221 (1956) 569-577.

2. Hartman, S.C. and Buchanan, J.M. Biosynthesis of the purines. XXII. 2-Amino-N-ribosylacetamide-5'-phosphate kinosynthase. J. Biol. Chem. 233 (1958) 456-461.

[EC 6.3.4.13 created 1961 as EC 6.3.1.3, transferred 1972 to EC 6.3.4.13, modified 2000]

EC 6.3.4.14

Accepted name: biotin carboxylase

Reaction: ATP + [biotin carboxyl-carrier protein]-biotin-N6-L-lysine + hydrogencarbonate- = ADP + phosphate + [biotin carboxyl-carrier protein]-carboxybiotin-N6-L-lysine

Other name(s): accC (gene name); biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming)

Systematic name: [biotin carboxyl-carrier protein]-biotin-N6-L-lysine:hydrogencarbonate ligase (ADP-forming)

Comments: This enzyme, part of an acetyl-CoA carboxylase complex, acts on a biotin carboxyl-carrier protein (BCCP) that has been biotinylated by EC 6.3.4.15, biotin—[biotin carboxyl-carrier protein] ligase. In some organisms the enzyme is part of a multi-domain polypeptide that also includes the carrier protein (e.g. mycobacteria). Yet in other organisms (e.g. mammals) this activity is included in a single polypeptide that also catalyses the transfer of the carboxyl group from biotin to acetyl-CoA (see EC 6.4.1.2, acetyl-CoA carboxylase).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9075-71-2

References:

1. Dimroth, P., Guchhait, R.B., Stoll, E. and Lane, M.D. Enzymatic carboxylation of biotin: molecular and catalytic properties of a component enzyme of acetyl CoA carboxylase. Proc. Natl. Acad. Sci. USA 67 (1970) 1353-1360. [PMID: 4922289]

2. Norman, E., De Smet, K.A., Stoker, N.G., Ratledge, C., Wheeler, P.R. and Dale, J.W. Lipid synthesis in mycobacteria: characterization of the biotin carboxyl carrier protein genes from Mycobacterium leprae and M. tuberculosis. J. Bacteriol. 176 (1994) 2525-2531. [PMID: 7909542]

3. Janiyani, K., Bordelon, T., Waldrop, G.L. and Cronan, J.E., Jr. Function of Escherichia coli biotin carboxylase requires catalytic activity of both subunits of the homodimer. J. Biol. Chem. 276 (2001) 29864-29870. [PMID: 11390406]

4. Chou, C.Y., Yu, L.P. and Tong, L. Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. J. Biol. Chem. 284 (2009) 11690-11697. [PMID: 19213731]

5. Broussard, T.C., Pakhomova, S., Neau, D.B., Bonnot, R. and Waldrop, G.L. Structural analysis of substrate, reaction intermediate, and product binding in Haemophilus influenzae biotin carboxylase. Biochemistry 54 (2015) 3860-3870. [PMID: 26020841]

[EC 6.3.4.14 created 1976, modified 2014, modified 2018]

EC 6.3.4.15

Accepted name: biotin—[biotin carboxyl-carrier protein] ligase

Reaction: ATP + biotin + [biotin carboxyl-carrier protein]-L-lysine = AMP + diphosphate + [biotin carboxyl-carrier protein]-N6-biotinyl-L-lysine

Other name(s): birA (gene name); HLCS (gene name); HCS1 (gene name); biotin-[acetyl-CoA carboxylase] synthetase; biotin-[acetyl coenzyme A carboxylase] synthetase; acetyl coenzyme A holocarboxylase synthetase; acetyl CoA holocarboxylase synthetase; biotin:apocarboxylase ligase; Biotin holoenzyme synthetase; biotin:apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming); biotin—[acetyl-CoA-carboxylase] ligase

Systematic name: biotin:apo-[carboxyl-carrier protein] ligase (AMP-forming)

Comments: The enzyme biotinylates a biotin carboxyl-carrier protein that is part of an acetyl-CoA carboxylase complex, enabling its subsequent carboxylation by EC 6.3.4.14, biotin carboxylase. The carboxyl group is eventually transferred to acetyl-CoA by EC 2.1.3.15, acetyl-CoA carboxytransferase. In some organisms the carrier protein is part of EC 6.4.1.2, acetyl-CoA carboxylase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37340-95-7

References:

1. Landman, A.D. and Dakshinamurti, K. Acetyl-Coenzyme A carboxylase. Role of the prosthetic group in enzyme polymerization. Biochem. J. 145 (1975) 545-548. [PMID: 239688]

2. Wilson, K.P., Shewchuk, L.M., Brennan, R.G., Otsuka, A.J. and Matthews, B.W. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc. Natl. Acad. Sci. USA 89 (1992) 9257-9261. [PMID: 1409631]

3. Nenortas, E. and Beckett, D. Purification and characterization of intact and truncated forms of the Escherichia coli biotin carboxyl carrier subunit of acetyl-CoA carboxylase. J. Biol. Chem. 271 (1996) 7559-7567. [PMID: 8631788]

[EC 6.3.4.15 created 1978, modified 2018]

EC 6.3.4.16

Accepted name: carbamoyl-phosphate synthase (ammonia)

Reaction: 2 ATP + NH3 + hydrogencarbonate = 2 ADP + phosphate + carbamoyl phosphate (overall reaction)
(1a) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1b) NH3 + carboxyphosphate = carbamate + phosphate
(1c) ATP + carbamate = ADP + carbamoyl phosphate

For diagram click here.

Other name(s): carbon-dioxide—ammonia ligase; carbamoylphosphate synthase; carbamylphosphate synthetase; carbamoylphosphate synthase (ammonia); carbamoylphosphate synthetase; carbamylphosphate synthetase I

Systematic name: carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating)

Comments: The enzyme catalyses the first committed step in the urea cycle. The reaction proceeds via three separate chemical reactions: phosphorylation of hydrogencarbonate to carboxyphosphate; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and the phosphorylation of carbamate forming carbamoyl phosphate. Two moles of ATP are utilized for the synthesis of one molecule of carbamyl phosphate, making the reaction essentially irreversible. The enzyme requires the allosteric activator N-acetyl-L-glutamate. cf. EC 6.3.5.5, carbamoyl-phosphate synthase (glutamine-hydrolysing).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9026-23-7

References:

1. Fahien, L.A. and Cohen, P.P. A kinetic study of carbamyl phosphate synthetase. J. Biol. Chem. 239 (1964) 1925-1934.

2. Jones, M.E. and Spector, L. The pathway of carbonate in the biosynthesis of carbamyl phosphate. J. Biol. Chem. 235 (1960) 2897-2901.

3. Marshall, M., Metzenberg, R.L. and Cohen, P.P. Purification of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 233 (1958) 102-105.

4. Marshall, M., Metzenberg, R.L. and Cohen, P.P. Physical and kinetic properties of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 236 (1961) 2229-2237.

[EC 6.3.4.16 created 1965 as EC 2.7.2.5, transferred 1978 to EC 6.3.4.16]

EC 6.3.4.17

Accepted name: formate—dihydrofolate ligase

Reaction: ATP + formate + dihydrofolate = ADP + phosphate + 10-formyldihydrofolate

Other name(s): formyltransferase, dihydrofolate; dihydrofolate formyltransferase; formyl dihydrofolate synthase

Systematic name: formate:dihydrofolate ligase (ADP-forming)

Comments: Not identical with EC 6.3.4.3 (formate—tetrahydrofolate ligase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 123303-25-3

References:

1. Drake, J.C., Baram, J. and Allegra, C.J. Isolation and characterization of a novel dihydrofolate formylating enzyme from human MCF-7 breast cancer cells. Biochem. Pharmacol. 39 (1990) 615-618. [PMID: 2306274]

[EC 6.3.4.17 created 1992]

EC 6.3.4.18

Accepted name: 5-(carboxyamino)imidazole ribonucleotide synthase

Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole + HCO3- = ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole

For diagram, click here

Other name(s): N5-CAIR synthetase; N5-carboxyaminoimidazole ribonucleotide synthetase; PurK

Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole:carbon-dioxide ligase (ADP-forming)

Comments: In Escherichia coli, this enzyme, along with EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp protein superfamily [3]. Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late stages of purine biosynthesis.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 255379-40-9

References:

1. Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway. Biochemistry 31 (1992) 5022-5032. [PMID: 1534690]

2. Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J. N5-Carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli. Biochemistry 33 (1994) 2269-2278. [PMID: 8117684]

3. Thoden, J.B., Kappock, T.J., Stubbe, J. and Holden, H.M. Three-dimensional structure of N5-carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily. Biochemistry 38 (1999) 15480-15492. [PMID: 10569930]

[EC 6.3.4.18 created 2006]

EC 6.3.4.19

Accepted name: tRNAIle-lysidine synthase

Reaction: [tRNAIle2]-cytidine34 + L-lysine + ATP = [tRNAIle2]-lysidine34 + AMP + diphosphate + H2O

Glossary: lysidine = N6-(4-amino-1-β-D-ribofuranosylpyrimidin-2-ylidene)-L-lysine

Other name(s): TilS; mesJ (gene name); yacA (gene name); isoleucine-specific transfer ribonucleate lysidine synthetase; tRNAIle-lysidine synthetase

Systematic name: L-lysine:[tRNAIle2]-cytidine34 ligase (AMP-forming)

Comments: The bacterial enzyme modifies the wobble base of the CAU anticodon of tRNAIle at the oxo group in position 2 of cytidine34. This modification determines both codon and amino acid specificities of tRNAIle.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Ikeuchi, Y., Soma, A., Ote, T., Kato, J., Sekine, Y. and Suzuki, T. molecular mechanism of lysidine synthesis that determines tRNA identity and codon recognition. Mol. Cell 19 (2005) 235-246. [PMID: 16039592]

2. Salowe, S.P., Wiltsie, J., Hawkins, J.C. and Sonatore, L.M. The catalytic flexibility of tRNAIle-lysidine synthetase can generate alternative tRNA substrates for isoleucyl-tRNA synthetase. J. Biol. Chem. 284 (2009) 9656-9662. [PMID: 19233850]

3. Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., Suzuki, T. and Nureki, O. Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. Proc. Natl. Acad. Sci. USA 102 (2005) 7487-7492. [PMID: 15894617]

4. Soma, A., Ikeuchi, Y., Kanemasa, S., Kobayashi, K., Ogasawara, N., Ote, T., Kato, J., Watanabe, K., Sekine, Y. and Suzuki, T. An RNA-modifying enzyme that governs both the codon and amino acid specificities of isoleucine tRNA. Mol. Cell 12 (2003) 689-698. [PMID: 14527414]

5. Nakanishi, K., Bonnefond, L., Kimura, S., Suzuki, T., Ishitani, R. and Nureki, O. Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase. Nature 461 (2009) 1144-1148. [PMID: 19847269]

[EC 6.3.4.19 created 2011]

EC 6.3.4.20

Accepted name: 7-cyano-7-deazaguanine synthase

Reaction: 7-carboxy-7-carbaguanine + NH3 + ATP = 7-cyano-7-carbaguanine + ADP + phosphate + H2O

For diagram of reaction click here.

Glossary: preQ0 = 7-cyano-7-carbaguanine = 7-cyano-7-deazaguanine
7-carboxy-7-carbaguanine = 7-carboxy-7-deazaguanine

Other name(s): preQ0 synthase; 7-cyano-7-carbaguanine synthase; queC (gene name)

Systematic name: 7-carboxy-7-carbaguanine:ammonia ligase (ADP-forming)

Comments: Binds Zn2+. The reaction is part of the biosynthesis pathway of queuosine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. McCarty, R.M., Somogyi, A., Lin, G., Jacobsen, N.E. and Bandarian, V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of preQ0 from guanosine 5'-triphosphate in four steps. Biochemistry 48 (2009) 3847-3852. [PMID: 19354300]

2. Cicmil, N. and Huang, R.H. Crystal structure of QueC from Bacillus subtilis: an enzyme involved in preQ1 biosynthesis. Proteins 72 (2008) 1084-1088. [PMID: 18491386]

[EC 6.3.4.20 created 2012]

EC 6.3.4.21

Accepted name: nicotinate phosphoribosyltransferase

Reaction: nicotinate + 5-phospho-α-D-ribose 1-diphosphate + ATP + H2O = β-nicotinate D-ribonucleotide + diphosphate + ADP + phosphate

For diagram of reaction click here.

Other name(s): niacin ribonucleotidase; nicotinic acid mononucleotide glycohydrolase; nicotinic acid mononucleotide pyrophosphorylase; nicotinic acid phosphoribosyltransferase; nicotinate-nucleotide:diphosphate phospho-α-D-ribosyltransferase

Systematic name: 5-phospho-α-D-ribose 1-diphosphate:nicotinate ligase (ADP, diphosphate-forming)

Comments: The enzyme, which is involved in pyridine nucleotide recycling, can form β-nicotinate D-ribonucleotide and diphosphate from nicotinate and 5-phospho-α-D-ribose 1-diphosphate (PRPP) in the absence of ATP. However, when ATP is available the enzyme is phosphorylated resulting in a much lower Km for nicotinate. The phospho-enzyme is hydrolysed during the transferase reaction, regenerating the low affinity form. The presence of ATP shifts the products/substrates equilibrium from 0.67 to 1100 [4].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9030-26-6

References:

1. Imsande, J. Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli. J. Biol. Chem. 236 (1961) 1494-1497. [PMID: 13717628]

2. Imsande, J. and Handler, P. Biosynthesis of diphosphopyridine nucleotide. III. Nicotinic acid mononucleotide pyrophosphorylase. J. Biol. Chem. 236 (1961) 525-530. [PMID: 13717627]

3. Kosaka, A., Spivey, H.O. and Gholson, R.K. Nicotinate phosphoribosyltransferase of yeast. Purification and properties. J. Biol. Chem. 246 (1971) 3277-3283. [PMID: 4324895]

4. Vinitsky, A. and Grubmeyer, C. A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate phosphoribosyltransferase. J. Biol. Chem. 268 (1993) 26004-26010. [PMID: 7503993]

[EC 6.3.4.21 created 1961 as EC 2.4.2.11, transferred 2013 to EC 6.3.4.21]

EC 6.3.4.22

Accepted name: tRNAIle2-agmatinylcytidine synthase

Reaction: ATP + agmatine + [tRNAIle2]-cytidine34 + H2O = [tRNAIle2]-2-agmatinylcytidine34 + AMP + 2 phosphate

Other name(s): TiaS; AF2259; tRNAIle-2-agmatinylcytidine synthetase; tRNAIle-agm2C synthetase; tRNAIle-agmatidine synthetase

Systematic name: agmatine:[tRNAIle]-cytidine34 ligase

Comments: The enzyme from the archaeon Archaeoglobus fulgidus modifies the wobble base of the CAU anticodon of the archaeal tRNAIle2 at the oxo group in position 2 of cytidine34. This modification is crucial for accurate decoding of the genetic code. In bacteria EC 6.3.4.19, tRNAIle-lysidine synthase, catalyses the modification of [tRNAIle2]-cytidine34 to [tRNAIle2]-lysidine34.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Ikeuchi, Y., Kimura, S., Numata, T., Nakamura, D., Yokogawa, T., Ogata, T., Wada, T., Suzuki, T. and Suzuki, T. Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea. Nat. Chem. Biol. 6 (2010) 277-282. [PMID: 20139989]

2. Terasaka, N., Kimura, S., Osawa, T., Numata, T. and Suzuki, T. Biogenesis of 2-agmatinylcytidine catalyzed by the dual protein and RNA kinase TiaS. Nat. Struct. Mol. Biol. 18 (2011) 1268-1274. [PMID: 22002222]

3. Osawa, T., Inanaga, H., Kimura, S., Terasaka, N., Suzuki, T. and Numata, T. Crystallization and preliminary X-ray diffraction analysis of an archaeal tRNA-modification enzyme, TiaS, complexed with tRNA(Ile2) and ATP. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 (2011) 1414-1416. [PMID: 22102245]

[EC 6.3.4.22 created 2013]

EC 6.3.4.23

Accepted name: formate—phosphoribosylaminoimidazolecarboxamide ligase

Reaction: ATP + formate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = ADP + phosphate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide

Other name(s): 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase; 5-formaminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5'-monophosphate synthetase; purP (gene name)

Systematic name: formate:5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide ligase (ADP-forming)

Comments: This archaeal enzyme, characterized from the methanogen Methanocaldococcus jannaschii, catalyses a step in the synthesis of purine nucleotides. It differs from the orthologous bacterial/eukaryotic enzymes, which utilize 10-formyltetrahydrofolate rather than formate and ATP. cf. EC 2.1.2.3, phosphoribosylaminoimidazolecarboxamide formyltransferase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Ownby, K., Xu, H. and White, R.H. A Methanocaldococcus jannaschii archaeal signature gene encodes for a 5-formaminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5'-monophosphate synthetase. A new enzyme in purine biosynthesis. J. Biol. Chem. 280 (2005) 10881-10887. [PMID: 15623504]

2. Zhang, Y., White, R.H. and Ealick, S.E. Crystal structure and function of 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase from Methanocaldococcus jannaschii. Biochemistry 47 (2008) 205-217. [PMID: 18069798]

[EC 6.3.4.23 created 2013]

EC 6.3.4.24

Accepted name: tyramine—L-glutamate ligase

Reaction: ATP + tyramine + L-glutamate = ADP + phosphate + γ-glutamyltyramine

For diagram of reaction click here.

Other name(s): mfnD (gene name)

Systematic name: tyramine:L-glutamate γ-ligase (ADP-forming)

Comments: The enzyme, which has been characterized from the archaebacterium Methanocaldococcus fervens, participates in the biosynthesis of the cofactor methanofuran. Requires a divalent cation for activity, with Mn2+ giving the highest activity, followed by Mg2+, Co2+, Zn2+, and Fe2+.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Wang, Y., Xu, H., Harich, K.C. and White, R.H. Identification and characterization of a tyramine-glutamate ligase (MfnD) Involved in methanofuran biosynthesis. Biochemistry 53 (2014) 6220-6230. [PMID: 25211225]

[EC 6.3.4.24 created 2014]


EC 6.3.5 Carbon—Nitrogen Ligases with Glutamine as Amido-N-Donor

Contents

EC 6.3.5.1 NAD+ synthase (glutamine-hydrolysing)
EC 6.3.5.2 GMP synthase (glutamine-hydrolysing)
EC 6.3.5.3 phosphoribosylformylglycinamidine synthase
EC 6.3.5.4 asparagine synthase (glutamine-hydrolysing)
EC 6.3.5.5 carbamoyl-phosphate synthase (glutamine-hydrolysing)
EC 6.3.5.6 asparaginyl-tRNA synthase (glutamine-hydrolysing)
EC 6.3.5.7 glutaminyl-tRNA synthase (glutamine-hydrolysing)
EC 6.3.5.8 now EC 2.6.1.85
EC 6.3.5.9 hydrogenobyrinic acid a,c-diamide synthase (glutamine-hydrolysing)
EC 6.3.5.10 adenosylcobyric acid synthase (glutamine-hydrolysing)
EC 6.3.5.11 cobyrinate a,c-diamide synthase
EC 6.3.5.12 Ni-sirohydrochlorin a,c-diamide synthase
EC 6.3.5.13 lipid II isoglutaminyl synthase (glutamine-hydrolysing)


Entries

EC 6.3.5.1

Accepted name: NAD+ synthase (glutamine-hydrolysing)

Reaction: ATP + deamido-NAD+ + L-glutamine + H2O = AMP + diphosphate + NAD+ + L-glutamate

For diagram of reaction click here

Other name(s): NAD synthetase (glutamine-hydrolysing); nicotinamide adenine dinucleotide synthetase (glutamine); desamidonicotinamide adenine dinucleotide amidotransferase; DPN synthetase

Systematic name: deamido-NAD+:L-glutamine amido-ligase (AMP-forming)

Comments: NH3 can act instead of glutamine (cf. EC 6.3.1.5 NAD+ synthase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-70-0

References:

1. Imsande, J. Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli. J. Biol. Chem. 236 (1961) 1494-1497.

2. Imsande, J. and Handler, P. Biosynthesis of diphosphopyridine nucleotide. III. Nicotinic acid mononucleotide pyrophosphorylase. J. Biol. Chem. 236 (1961) 525-530.

[EC 6.3.5.1 created 1961]

EC 6.3.5.2

Accepted name: GMP synthase (glutamine-hydrolysing)

Reaction: ATP + XMP + L-glutamine + H2O = AMP + diphosphate + GMP + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + XMP + NH3 = AMP + diphosphate + GMP

For diagram of reaction click here.

Glossary: XMP = xanthosine 5'-phosphate

Other name(s): GMP synthetase (glutamine-hydrolysing); guanylate synthetase (glutamine-hydrolyzing); guanosine monophosphate synthetase (glutamine-hydrolyzing); xanthosine 5'-phosphate amidotransferase; guanosine 5'-monophosphate synthetase

Systematic name: xanthosine-5'-phosphate:L-glutamine amido-ligase (AMP-forming)

Comments: Involved in the de novo biosynthesis of guanosine nucleotides. An N-terminal glutaminase domain binds L-glutamine and generates ammonia, which is transferred by a substrate-protective tunnel to the ATP-pyrophosphatase domain. The enzyme can catalyse the second reaction alone in the presence of ammonia.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-71-1

References:

1. Lagerkvist, U. Biosynthesis of guanosine 5'-phosphate. II. Amination of xanthosine 5'-phosphate by purified enzyme from pigeon liver. J. Biol. Chem. 233 (1958) 143-149. [PMID: 13563458]

2. Abrams, R. and Bentley, M. Biosynthesis of nucleic acid purines. III. Guanosine 5'-phosphate formation from xanthosine 5'-phosphate and L-glutamine. Arch. Biochem. Biophys. 79 (1959) 91-110.

3. Zalkin, H., Argos, P., Narayana, S.V., Tiedeman, A.A. and Smith, J.M. Identification of a trpG-related glutamine amide transfer domain in Escherichia coli GMP synthetase. J. Biol. Chem. 260 (1985) 3350-3354. [PMID: 2982857]

4. Abbott, J.L., Newell, J.M., Lightcap, C.M., Olanich, M.E., Loughlin, D.T., Weller, M.A., Lam, G., Pollack, S. and Patton, W.A. The effects of removing the GAT domain from E. coli GMP synthetase. Protein J. 25 (2006) 483-491. [PMID: 17103135]

[EC 6.3.5.2 created 1961, modified 2013]

EC 6.3.5.3

Accepted name: phosphoribosylformylglycinamidine synthase

Reaction: ATP + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H2O = ADP + phosphate + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine + L-glutamate

For reaction pathway click here.

Other name(s): phosphoribosylformylglycinamidine synthetase; formylglycinamide ribonucloetide amidotransferase; phosphoribosylformylglycineamidine synthetase; FGAM synthetase; FGAR amidotransferase

Systematic name: N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide:L-glutamine amido-ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-84-2

References:

1. Melnick, I. and Buchanan, J.M. Biosynthesis of the purines. I. Conversion of (α-N-formyl)glycinamide ribotide to (α-N-formyl)glycinamidine ribotide; purification and requirements of the enzyme system. J. Biol. Chem. 225 (1957) 157-162.

[EC 6.3.5.3 created 1961, modified 2000]

EC 6.3.5.4

Accepted name: asparagine synthase (glutamine-hydrolysing)

Reaction: ATP + L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine

Other name(s): asparagine synthetase (glutamine-hydrolysing); glutamine-dependent asparagine synthetase; asparagine synthetase B; AS; AS-B

Systematic name: L-aspartate:L-glutamine amido-ligase (AMP-forming)

Comments: The enzyme from Escherichia coli has two active sites [4] that are connected by an intramolecular ammonia tunnel [6,7]. The enzyme catalyses three distinct chemical reactions: glutamine hydrolysis to yield ammonia takes place in the N-terminal domain. The C-terminal active site mediates both the synthesis of a β-aspartyl-AMP intermediate and its subsequent reaction with ammonia. The ammonia released is channeled to the other active site to yield asparagine [7].

Links to other databases: BRENDA, EXPASY, KEGG, PDB, Metacyc, PDB, CAS registry number: 37318-72-2

References:

1. Patterson, M.K., Jr. and Orr, G.R. Asparagine biosynthesis by the Novikoff hepatoma. Isolation, purification, property, and mechanism studies of the enzyme system. J. Biol. Chem. 243 (1968) 376-380. [PMID: 4295091]

2. Boehlein, S.K., Richards, N.G. and Schuster, S.M. Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. J. Biol. Chem. 269 (1994) 7450-7457. [PMID: 7907328]

3. Richards, N.G. and Schuster, S.M. Mechanistic issues in asparagine synthetase catalysis. Adv. Enzymol. Relat. Areas Mol. Biol. 72 (1998) 145-198. [PMID: 9559053]

4. Larsen, T.M., Boehlein, S.K., Schuster, S.M., Richards, N.G., Thoden, J.B., Holden, H.M. and Rayment, I. Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry 38 (1999) 16146-16157. [PMID: 10587437]

5. Huang, X., Holden, H.M. and Raushel, F.M. Channeling of substrates and intermediates in enzyme-catalyzed reactions. Annu. Rev. Biochem. 70 (2001) 149-180. [PMID: 11395405]

6. Tesson, A.R., Soper, T.S., Ciustea, M. and Richards, N.G. Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli. Arch. Biochem. Biophys. 413 (2003) 23-31. [PMID: 12706338]

[EC 6.3.5.4 created 1972, modified 2006]

EC 6.3.5.5

Accepted name: carbamoyl-phosphate synthase (glutamine-hydrolysing)

Reaction: 2 ATP + L-glutamine + hydrogencarbonate + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1c) NH3 + carboxyphosphate = carbamate + phosphate
(1d) ATP + carbamate = ADP + carbamoyl phosphate

For diagram of reaction click here.

Other name(s): carbamoyl-phosphate synthetase (glutamine-hydrolysing); carbamyl phosphate synthetase (glutamine); carbamoylphosphate synthetase II; glutamine-dependent carbamyl phosphate synthetase; carbamoyl phosphate synthetase; CPS; carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating); carA (gene name); carB (gene name); CAD (gene name); hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)

Systematic name: hydrogencarbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)

Comments: The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 Å in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxyphosphate to produce the carbamate intermediate. The carboxyphosphate intermediate is formed by the phosphorylation of hydrogencarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6]. cf. EC 6.3.4.16, carbamoyl-phosphate synthase (ammonia).

Links to other databases: BRENDA, EXPASY, KEGG, PDB, Metacyc, PDB, CAS registry number: 37233-48-0

References:

1. Anderson, P.M. and Meister, A. Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase. Biochemistry 4 (1965) 2803-2809.

2. Kalman, S.M., Duffield, P.H. and Brzozowski, T. Purification and properties of a bacterial carbamyl phosphate synthetase. J. Biol. Chem. 241 (1966) 1871-1877. [PMID: 5329589]

3. Yip, M.C.M. and Knox, W.E. Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues. J. Biol. Chem. 245 (1970) 2199-2204. [PMID: 5442268]

4. Stapleton, M.A., Javid-Majd, F., Harmon, M.F., Hanks, B.A., Grahmann, J.L., Mullins, L.S. and Raushel, F.M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry 35 (1996) 14352-14361. [PMID: 8916922]

5. Holden, H.M., Thoden, J.B. and Raushel, F.M. Carbamoyl phosphate synthetase: a tunnel runs through it. Curr. Opin. Struct. Biol. 8 (1998) 679-685. [PMID: 9914247]

6. Raushel, F.M., Thoden, J.B., Reinhart, G.D. and Holden, H.M. Carbamoyl phosphate synthetase: a crooked path from substrates to products. Curr. Opin. Chem. Biol. 2 (1998) 624-632. [PMID: 9818189]

7. Raushel, F.M., Thoden, J.B. and Holden, H.M. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry 38 (1999) 7891-7899. [PMID: 10387030]

8. Thoden, J.B., Huang, X., Raushel, F.M. and Holden, H.M. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J. Biol. Chem. 277 (2002) 39722-39727. [PMID: 12130656]

[EC 6.3.5.5 created 1972 as EC 2.7.2.9, transferred 1978 to EC 6.3.5.5, modified 2006]

EC 6.3.5.6

Accepted name: asparaginyl-tRNA synthase (glutamine-hydrolysing)

Reaction: ATP + L-aspartyl-tRNAAsn + L-glutamine + H2O = ADP + phosphate + L-asparaginyl-tRNAAsn + L-glutamate
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + L-aspartyl-tRNAAsn = ADP + 4-phosphooxy-L-aspartyl-tRNAAsn
(1c) 4-phosphooxy-L-aspartyl-tRNAAsn + NH3 = L-asparaginyl-tRNAAsn + phosphate

Other name(s): Asp-AdT; Asp-tRNAAsn amidotransferase; aspartyl-tRNAAsn amidotransferase; Asn-tRNAAsn:L-glutamine amido-ligase (ADP-forming); aspartyl-tRNAAsn:L-glutamine amido-ligase (ADP-forming); GatCAB

Systematic name: L-aspartyl-tRNAAsn:L-glutamine amido-ligase (ADP-forming)

Comments: This reaction forms part of a two-reaction system for producing asparaginyl-tRNA in Deinococcus radiodurans and other organisms lacking a specific enzyme for asparagine synthesis. In the first step, a non-discriminating ligase (EC 6.1.1.23, aspartate—tRNAAsn ligase) mischarges tRNAAsn with aspartate, leading to the formation of aspartyl-tRNAAsn. The aspartyl-tRNAAsn is not used in protein synthesis until the present enzyme converts it into asparaginyl-tRNAAsn (aspartyl-tRNAAsp is not a substrate for this enzyme). A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 30 Å tunnel to a synthase subunit, where it is ligated to the carboxy group that has been activated by phosphorylation. Bacterial GatCAB complexes also has the activity of EC 6.3.5.7 (glutaminyl-tRNA synthase [glutamine-hydrolysing]).

Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, CAS registry number: 37211-76-0

References:

1. Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNAGln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838-12843. [PMID: 9789001]

2. Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617-650. [PMID: 10966471]

3. Min, B., Pelaschier, J.T., Graham, D.E., Tumbula-Hansen, D. and Söll, D. Transfer RNA-dependent amino acid biosynthesis: an essential route to asparagine formation. Proc. Natl. Acad. Sci. USA 99 (2002) 2678-2683. [PMID: 11880622]

[EC 6.3.5.6 created 2002, modified 2012, modified 2019]

EC 6.3.5.7

Accepted name: glutaminyl-tRNA synthase (glutamine-hydrolysing)

Reaction: ATP + L-glutamyl-tRNAGln + L-glutamine = ADP + phosphate + L-glutaminyl-tRNAGln + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + L-glutamyl-tRNAGln = ADP + 5-phosphooxy-L-glutamyl-tRNAGln
(1c) 5-phosphooxy-L-glutamyl-tRNAGln + NH3 = L-glutaminyl-tRNAGln + phosphate

Other name(s): Glu-AdT; Glu-tRNAGln amidotransferase; glutamyl-tRNAGln amidotransferase; Glu-tRNAGln:L-glutamine amido-ligase (ADP-forming); GatCAB; GatFAB; GatDE

Systematic name: L-glutamyl-tRNAGln:L-glutamine amido-ligase (ADP-forming)

Comments: In systems lacking discernible glutamine—tRNA ligase (EC 6.1.1.18), glutaminyl-tRNAGln is formed by a two-enzyme system. In the first step, a nondiscriminating ligase (EC 6.1.1.24, glutamate—tRNAGln ligase) mischarges tRNAGln with glutamate, forming glutamyl-tRNAGln. The glutamyl-tRNAGln is not used in protein synthesis until the present enzyme converts it into glutaminyl-tRNAGln (glutamyl-tRNAGlu is not a substrate for this enzyme). A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 30 Å tunnel to a synthase subunit, where it is ligated to the carboxy group that has been activated by phosphorylation. Some bacterial GatCAB complexes also has the activity of EC 6.3.5.6 (asparaginyl-tRNA synthase [glutamine-hydrolysing]).

Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, CAS registry number: 52232-48-1

References:

1. Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNAGln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838-12843. [PMID: 9789001]

2. Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617-650. [PMID: 10966471]

3. Raczniak, G., Becker, H.D., Min, B. and Soll, D. A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia trachomatis. J. Biol. Chem 276 (2001) 45862-45867. [PMID: 11585842]

4. Horiuchi, K.Y., Harpel, M.R., Shen, L., Luo, Y., Rogers, K.C. and Copeland, R.A. Mechanistic studies of reaction coupling in Glu-tRNAGln amidotransferase. Biochemistry 40 (2001) 6450-6457. [PMID: 11371208]

5. Feng, L., Sheppard, K., Tumbula-Hansen, D. and Soll, D. Gln-tRNAGln formation from Glu-tRNAGln requires cooperation of an asparaginase and a Glu-tRNAGln kinase. J. Biol. Chem 280 (2005) 8150-8155. [PMID: 15611111]

6. Nakamura, A., Yao, M., Chimnaronk, S., Sakai, N. and Tanaka, I. Ammonia channel couples glutaminase with transamidase reactions in GatCAB. Science 312 (2006) 1954-1958. [PMID: 16809541]

7. Wu, J., Bu, W., Sheppard, K., Kitabatake, M., Kwon, S.T., Soll, D. and Smith, J.L. Insights into tRNA-dependent amidotransferase evolution and catalysis from the structure of the Aquifex aeolicus enzyme. J. Mol. Biol. 391 (2009) 703-716. [PMID: 19520089]

8. Araiso, Y., Huot, J.L., Sekiguchi, T., Frechin, M., Fischer, F., Enkler, L., Senger, B., Ishitani, R., Becker, H.D. and Nureki, O. Crystal structure of Saccharomyces cerevisiae mitochondrial GatFAB reveals a novel subunit assembly in tRNA-dependent amidotransferases. Nucleic Acids Res. 42 (2014) 6052-6063. [PMID: 24692665]

[EC 6.3.5.7 created 2002, modified 2019]

[EC 6.3.5.8 Transferred entry: Now EC 2.6.1.85, aminodeoxychorismate synthase. As ATP is not hydrolysed during the reaction, the classification of the enzyme as a ligase was incorrect. (EC 6.3.5.8 created 2003, deleted 2007)]

EC 6.3.5.9

Accepted name: hydrogenobyrinic acid a,c-diamide synthase (glutamine-hydrolysing)

Reaction: 2 ATP + hydrogenobyrinic acid + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + hydrogenobyrinic acid a,c-diamide + 2 L-glutamate

For diagram click here.

Other name(s): CobB

Systematic name: hydrogenobyrinic-acid:L-glutamine amido-ligase (AMP-forming)

Comments: This step in the aerobic biosynthesis of cobalamin generates hydrogenobyrinic acid a,c-diamide, the substrate required by EC 6.6.1.2, cobaltochelatase, which adds cobalt to the macrocycle.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 132053-22-6

References:

1. Debussche, L., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Purification and characterization of cobyrinic acid a,c-diamide synthase from Pseudomonas denitrificans. J. Bacteriol. 172 (1990) 6239-6244. [PMID: 2172209]

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]

[EC 6.3.5.9 created 2004]

EC 6.3.5.10

Accepted name: adenosylcobyric acid synthase (glutamine-hydrolysing)

Reaction: 4 ATP + adenosylcobyrinic acid a,c-diamide + 4 L-glutamine + 4 H2O = 4 ADP + 4 phosphate + adenosylcobyric acid + 4 L-glutamate

For diagram click here.

Other name(s): CobQ; cobyric acid synthase; 5'-deoxy-5'-adenosylcobyrinic-acid-a,c-diamide:L-glutamine amido-ligase; Ado-cobyric acid synthase [glutamine hydrolyzing]

Systematic name: adenosylcobyrinic-acid-a,c-diamide:L-glutamine amido-ligase (ADP-forming)

Comments: Requires Mg2+. NH3 can act instead of glutamine. This enzyme catalyses the four-step amidation sequence from cobyrinic acid a,c-diamide to cobyric acid via the formation of cobyrinic acid triamide, tetraamide and pentaamide intermediates.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 137672-90-3

References:

1. Blanche, F., Couder, M., Debussche, L., Thibaut, D., Cameron, B. and Crouzet, J. Biosynthesis of vitamin B12: stepwise amidation of carboxyl groups b, d, e, and g of cobyrinic acid a,c-diamide is catalyzed by one enzyme in Pseudomonas denitrificans. J. Bacteriol. 173 (1991) 6046-6051. [PMID: 1917839]

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]

[EC 6.3.5.10 created 2004]

EC 6.3.5.11

Accepted name: cobyrinate a,c-diamide synthase

Reaction: 2 ATP + cobyrinate + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + cobyrinate a,c-diamide + 2 L-glutamate
(1a) ATP + cobyrinate + L-glutamine + H2O = ADP + phosphate + cobyrinate c-monamide + L-glutamate
(1b) ATP + cobyrinate c-monamide + L-glutamine + H2O = ADP + phosphate + cobyrinate a,c-diamide + L-glutamate

For diagram click here.

Other name(s): cobyrinic acid a,c-diamide synthetase; CbiA (gene name)

Comments: This enzyme is the first glutamine amidotransferase that participates in the anaerobic (early cobalt insertion) biosynthetic pathway of adenosylcobalamin, and catalyses the ATP-dependent synthesis of cobyrinate a,c-diamide from cobyrinate using either L-glutamine or ammonia as the nitrogen source. It is proposed that the enzyme first catalyses the amidation of the c-carboxylate, and then the intermediate is released into solution and binds to the same catalytic site for the amidation of the a-carboxylate. The Km for ammonia is substantially higher than that for L-glutamine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Fresquet, V., Williams, L. and Raushel, F.M. Mechanism of cobyrinic acid a,c-diamide synthetase from Salmonella typhimurium LT2. Biochemistry 43 (2004) 10619-10627. [PMID: 15311923]

[EC 6.3.5.11 created 2010]

EC 6.3.5.12

Accepted name: Ni-sirohydrochlorin a,c-diamide synthase

Reaction: 2 ATP + Ni-sirohydrochlorin + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + Ni-sirohydrochlorin a,c-diamide + 2 L-glutamate

For diagram of reaction click here.

Other name(s): cfbB (gene name)

Systematic name: Ni-sirohydrochlorin:L-glutamine amido-ligase (ADP-forming)

Comments: The enzyme, studied from the methanogenic archaeon Methanosarcina acetivorans, participates in the biosynthesis of the nickel-containing tetrapyrrole cofactor coenzyme F430, which is required by EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Zheng, K., Ngo, P.D., Owens, V.L., Yang, X.P. and Mansoorabadi, S.O. The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354 (2016) 339-342. [PMID: 27846569]

[EC 6.3.5.12 created 2017]

EC 6.3.5.13

Accepted name: lipid II isoglutaminyl synthase (glutamine-hydrolysing)

Reaction: ATP + β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol + L-glutamine + H2O = ADP + phosphate + β-D-GlcNAc-(1→4)-MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol = ADP + β-D-GlcNAc-(1→4)-MurNAc-L-Ala-γ-D-O-P-Glu-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol
(1c) β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-O-P-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol + NH3 = β-D-GlcNAc-(1→4)-MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol + phosphate

Glossary: lipid II = undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl peptide; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof = undecaprenyldiphospho-4-O-(N-acetyl-β-D-glucosaminyl)-3-O-peptidyl-α-N-acetylmuramate; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof

Other name(s): MurT/GatD; MurT/GatD complex

Systematic name: β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol:L-glutamine amidoligase (ADP-forming)

Comments: The enzyme complex, found in Gram-positive bacteria, consists of two subunits. A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is channeled to a ligase subunit, which adds it to the activated D-glutamate residue of lipid II, converting it to an isoglutamine residue.

Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, CAS registry number:

References:

1. Munch, D., Roemer, T., Lee, S.H., Engeser, M., Sahl, H.G. and Schneider, T. Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus. PLoS Pathog. 8 (2012) e1002509. [PMID: 22291598]

2. Noldeke, E.R., Muckenfuss, L.M., Niemann, V., Muller, A., Stork, E., Zocher, G., Schneider, T. and Stehle, T. Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus. Sci Rep 8 (2018) 12953. [PMID: 30154570]

3. Morlot, C., Straume, D., Peters, K., Hegnar, O.A., Simon, N., Villard, A.M., Contreras-Martel, C., Leisico, F., Breukink, E., Gravier-Pelletier, C., Le Corre, L., Vollmer, W., Pietrancosta, N., Havarstein, L.S. and Zapun, A. Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Nat Commun 9 (2018) 3180. [PMID: 30093673]

[EC 6.3.5.13 created 2019]


Continued with EC 6.4.1.1 to EC 6.5.1.4
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