Enzyme Nomenclature

EC 2.3.2

Aminoacyltransferases

Continued from EC 2.3.1.200 to EC 2.3.1.291

Contents

EC 2.3.2.1 D-glutamyltransferase
EC 2.3.2.2 γ-glutamyltransferase
EC 2.3.2.3 lysyltransferase
EC 2.3.2.4 transferred now EC 4.3.2.9
EC 2.3.2.5 glutaminyl-peptide cyclotransferase
EC 2.3.2.6 lysine/arginine leucyltransferase
EC 2.3.2.7 aspartyltransferase
EC 2.3.2.8 arginyltransferase
EC 2.3.2.9 agaritine γ-glutamyltransferase
EC 2.3.2.10 UDP-N-acetylmuramoylpentapeptide-lysine N6-alanyltransferase
EC 2.3.2.11 alanylphosphatidylglycerol synthase
EC 2.3.2.12 peptidyltransferase
EC 2.3.2.13 protein-glutamine γ-glutamyltransferase
EC 2.3.2.14 D-alanine γ-glutamyltransferase
EC 2.3.2.15 glutathione γ-glutamylcysteinyltransferase
EC 2.3.2.16 lipid II:glycine glycyltransferase
EC 2.3.2.17 N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase
EC 2.3.2.18 N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-triglycine)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase
EC 2.3.2.19 ribostamycin:4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase
EC 2.3.2.20 cyclo(L-leucyl-L-phenylalanyl) synthase
EC 2.3.2.21 cyclo(L-tyrosyl-L-tyrosyl) synthase
EC 2.3.2.22 cyclo(L-leucyl-L-leucyl) synthase
EC 2.3.2.23 E2 ubiquitin-conjugating enzyme
EC 2.3.2.24 (E3-independent) E2 ubiquitin-conjugating enzyme
EC 2.3.2.25 N-terminal E2 ubiquitin-conjugating enzyme
EC 2.3.2.26 HECT-type E3 ubiquitin transferase
EC 2.3.2.27 RING-type E3 ubiquitin transferase
EC 2.3.2.28 L-allo-isoleucyltransferase
EC 2.3.2.29 aspartate/glutamate leucyltransferase
EC 2.3.2.30 L-ornithine Nα-acyltransferase
EC 2.3.2.31 RBR-type E3 ubiquitin transferase
EC 2.3.2.32 cullin-RING-type E3 NEDD8 transferase

Entries

EC 2.3.2.1

Accepted name: D-glutamyltransferase

Reaction: (1) D-glutamine + D-glutamate = NH3 + γ-D-glutamyl-D-glutamate
(2) L(or D)-glutamine + (γ-D-glutamyl)n-[peptide] = ammonia + (γ-D-glutamyl)n+1-[peptide]

Other name(s): D-glutamyl transpeptidase; D-γ-glutamyl transpeptidase

Systematic name: L(or D)-glutamine

Comments: The enzyme catalyses two reactions. The first is the transfer of a glutamyl residue from L- or D-glutamine to D-glutamate via a γ linkage, forming γ-glutamyl-D-glutamate, and the second is the transfer of additional glutamyl residues to the peptide, extending the polypeptide chain.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9030-02-8

References:

1. Williams, W.J. and Thorne, C.B. Biosynthesis of glutamyl peptides from glutamine by a transfer reaction. J. Biol. Chem. 210 (1954) 203-217. [PMID: 13201582]

2. Williams, W.J., Litwin, J. and Thorne, C.B. Further studies on the biosynthesis of γ-glutamyl peptides by transfer reactions. J. Biol. Chem. 212 (1955) 427-438. [PMID: 13233245]

[EC 2.3.2.1 created 1961, modified 1976, modified 2013]

EC 2.3.2.2

Accepted name: γ-glutamyltransferase

Reaction: a (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid

Other name(s): glutamyl transpeptidase; α-glutamyl transpeptidase; γ-glutamyl peptidyltransferase; γ-glutamyl transpeptidase (ambiguous); γ-GPT; γ-GT; γ-GTP; L-γ-glutamyl transpeptidase; L-γ-glutamyltransferase; L-glutamyltransferase; GGT (ambiguous); γ-glutamyltranspeptidase (ambiguous)

Systematic name: (5-L-glutamyl)-peptide:amino-acid 5-glutamyltransferase

Comments: The mammlian enzyme is part of the cell antioxidant defense mechanism. It initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracelular GSH levels. The protein also has EC 3.4.19.13 (glutathione hydrolase) activity [3-4]. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide. The N-terminal L-threonine of the C-terminal subunit functions as the active site for both the cleavage and the hydrolysis reactions [3-4].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9046-27-9

References:

1. Goore, M.Y. and Thompson, J.F. γ-Glutamyl transpeptidase from kidney bean fruit. I. Purification and mechanism of action. Biochim. Biophys. Acta 132 (1967) 15-26. [PMID: 6030345]

2. Leibach, F.H. and Binkley, F. γ-Glutamyl transferase of swine kidney. Arch. Biochem. Biophys. 127 (1968) 292-301. [PMID: 5698023]

3. Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471-6476. [PMID: 16618936]

4. Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534-541. [PMID: 17107958]

5. Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208-214. [PMID: 21447318]

[EC 2.3.2.2 created 1972, modified 1976, modified 2011]

EC 2.3.2.3

Accepted name: lysyltransferase

Reaction: L-lysyl-tRNALys + phosphatidylglycerol = tRNALys + 3-O-L-lysyl-1-O-phosphatidylglycerol

Other name(s): L-lysyl-tRNA:phosphatidylglycerol 3-O-lysyltransferase

Systematic name: L-lysyl-tRNALys:phosphatidylglycerol 3-O-lysyltransferase

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-20-8

References:

1. Lennarz, W.J., Bonsen, P.P.M. and van Deenan, L.L.M. Substrate specificity of O-L-lysylphosphatidylglycerol synthetase. Enzymatic studies on the structure of O-L-lysylphosphatidylglycerol. Biochemistry 6 (1967) 2307-2312. [PMID: 6049461]

[EC 2.3.2.3 created 1972, modified 2013]

[EC 2.3.2.4 Transferred entry: γ-glutamylcyclotransferase. Now classified as EC 4.3.2.9, γ-glutamylcyclotransferase (EC 2.3.2.4 created 1972, deleted 2017)]

EC 2.3.2.5

Accepted name: glutaminyl-peptide cyclotransferase

Reaction: L-glutaminyl-peptide = 5-oxoprolyl-peptide + NH3

Other name(s): glutaminyl-tRNA cyclotransferase; glutaminyl cyclase; glutaminyl-transfer ribonucleate cyclotransferase

Systematic name: L-glutaminyl-peptide γ-glutamyltransferase (cyclizing)

Comments: Involved in the formation of thyrotropin-releasing hormone and other biologically active peptides containing N-terminal pyroglutamyl residues. The enzyme from papaya also acts on glutaminyl-tRNA.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37257-21-9

References:

1. Busby, W.H., Quackenbush, G.E., Humm, J., Youngblood, W.W. and Kizer, J.S. An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes. J. Biol. Chem. 262 (1987) 8532-8536. [PMID: 3597387]

2. Fischer, W.H. and Spiess, J. Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. Proc. Natl. Acad. Sci. USA 84 (1987) 3628-3632. [PMID: 3473473]

3. Messer, M. and Ottesen, M. Isolation and properties of glutamine cyclotransferase of dried papaya latex. C.R. Trav. Lab. Carlsberg 35 (1965) 1-24.

[EC 2.3.2.5 created 1972, modified 1990]

EC 2.3.2.6

Accepted name: lysine/arginine leucyltransferase

Reaction: (1) L-leucyl-tRNALeu + N-terminal L-lysyl-[protein] = tRNALeu + N-terminal L-leucyl-L-lysyl-[protein]
(2) L-leucyl-tRNALeu + N-terminal L-arginyl-[protein] = tRNALeu + N-terminal L-leucyl-L-arginyl-[protein]

Other name(s): leucyl, phenylalanine-tRNA-protein transferase; leucyl-phenylalanine-transfer ribonucleate-protein aminoacyltransferase; leucyl-phenylalanine-transfer ribonucleate-protein transferase; L-leucyl-tRNA:protein leucyltransferase; leucyltransferase (misleading); L/FK,R-transferase; aat (gene name); L-leucyl-tRNALeu:protein leucyltransferase

Systematic name: L-leucyl-tRNALeu:[protein] N-terminal L-lysine/L-arginine leucyltransferase

Comments: Requires a univalent cation. The enzyme participates in the N-end rule protein degradation pathway in certain bacteria, by attaching the primary destabilizing residue L-leucine to the N-termini of proteins that have an N-terminal L-arginine or L-lysine residue. Once modified, the proteins are recognized by EC 3.4.21.92, the ClpAP/ClpS endopeptidase system. The enzyme also transfers L-phenylalanine in vitro, but this has not been observed in vivo [5]. cf. EC 2.3.2.29, aspartate/glutamate leucyltransferase, and EC 2.3.2.8, arginyltransferase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37257-22-0

References:

1. Leibowitz, M.J. and Soffer, R.L. A soluble enzyme from Escherichia coli which catalyzes the transfer of leucine and phenylalanine from tRNA to acceptor proteins. Biochem. Biophys. Res. Commun. 36 (1969) 47-53. [PMID: 4894363]

2. Leibowitz, M.J. and Soffer, R.L. Enzymatic modification of proteins. 3. Purification and properties of a leucyl, phenylalanyl transfer ribonucleic acid protein transferase from Escherichia coli. J. Biol. Chem. 245 (1970) 2066-2073. [PMID: 4909560]

3. Soffer, R.L. Peptide acceptors in the leucine, phenylalanine transfer reaction. J. Biol. Chem. 248 (1973) 8424-8428. [PMID: 4587124]

4. Tobias, J.W., Shrader, T.E., Rocap, G. and Varshavsky, A. The N-end rule in bacteria. Science 254 (1991) 1374-1377. [PMID: 1962196]

5. Shrader, T.E., Tobias, J.W. and Varshavsky, A. The N-end rule in Escherichia coli: cloning and analysis of the leucyl, phenylalanyl-tRNA-protein transferase gene aat. J. Bacteriol. 175 (1993) 4364-4374. [PMID: 8331068]

6. Abramochkin, G. and Shrader, T.E. The leucyl/phenylalanyl-tRNA-protein transferase. Overexpression and characterization of substrate recognition, domain structure, and secondary structure. J. Biol. Chem. 270 (1995) 20621-20628. [PMID: 7657641]

[EC 2.3.2.6 created 1972, modified 1976, modified 2013, modified 2016]

EC 2.3.2.7

Accepted name: aspartyltransferase

Reaction: L-asparagine + hydroxylamine = NH3 + β-L-aspartylhydroxamate

Other name(s): β-aspartyl transferase; aspartotransferase

Systematic name: L-asparagine:hydroxylamine γ-aspartyltransferase

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-23-1

References:

1. Jayaram, H.N., Ramakrishnan, T. and Vaidyanathan, C.S. Aspartotransferase from Mycobacterium tuberculosis H37Ra. Indian J. Biochem. 6 (1969) 106-110.

[EC 2.3.2.7 created 1972]

EC 2.3.2.8

Accepted name: arginyltransferase

Reaction: L-arginyl-tRNAArg + protein = tRNAArg + L-arginyl-[protein]

Other name(s): arginine transferase; arginyl-transfer ribonucleate-protein aminoacyltransferase; arginyl-transfer ribonucleate-protein transferase; arginyl-tRNA protein transferase; L-arginyl-tRNA:protein arginyltransferase

Systematic name: L-arginyl-tRNAArg:protein arginyltransferase

Comments: Requires mercaptoethanol and a univalent cation. Peptides and proteins containing an N-terminal glutamate, aspartate or cystine residue can act as acceptors.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-24-2

References:

1. Soffer, R.L. Enzymatic modification of proteins. II. Purification and properties of the arginyl transfer ribonucleic acid-protein transferase from rabbit liver cytoplasm. J. Biol. Chem. 245 (1970) 731-737. [PMID: 5416661]

2. Soffer, R.L. Peptide acceptors in the arginine transfer reaction. J. Biol. Chem. 248 (1973) 2918-2921. [PMID: 4572514]

3. Soffer, R.L. and Horinishi, H. Enzymic modification of proteins. I. General characteristics of the arginine-transfer reaction in rabbit liver cytoplasm. J. Mol. Biol. 43 (1969) 163-175. [PMID: 5811819]

[EC 2.3.2.8 created 1972, modified 1976, modified 2013]

EC 2.3.2.9

Accepted name: agaritine γ-glutamyltransferase

Reaction: agaritine + acceptor = 4-hydroxymethylphenylhydrazine + γ-L-glutamyl-acceptor

Other name(s): (γ-L-glutamyl)-N1-(4-hydroxymethylphenyl)hydrazine:(acceptor) γ-glutamyltransferase

Systematic name: (γ-L-glutamyl)-N1-(4-hydroxymethylphenyl)hydrazine:acceptor γ-glutamyltransferase

Comments: 4-Hydroxyaniline, cyclohexylamine, 1-naphthylhydrazine and similar compounds can act as acceptors; the enzyme also catalyses the hydrolysis of agaritine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-25-3

References:

1. Gigliotti, H.J. and Levenberg, B. Studies on the γ-glutamyltransferase of Agaricus bisporus. J. Biol. Chem. 239 (1964) 2274-2284.

[EC 2.3.2.9 created 1972]

EC 2.3.2.10

Accepted name: UDP-N-acetylmuramoylpentapeptide-lysine N6-alanyltransferase

Reaction: L-alanyl-tRNAAla + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine = tRNAAla + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamyl-N6-(L-alanyl)-L-lysyl-D-alanyl-D-alanine

Other name(s): alanyl-transfer ribonucleate-uridine diphosphoacetylmuramoylpentapeptide transferase; UDP-N-acetylmuramoylpentapeptide lysine N6-alanyltransferase; uridine diphosphoacetylmuramoylpentapeptide lysine N6-alanyltransferase; L-alanyl-tRNA:UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine 6-N-alanyltransferase; L-alanyl-tRNA:UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine N6-alanyltransferase

Systematic name: L-alanyl-tRNAAla:UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine N6-alanyltransferase

Comments: Also acts on L-seryl-tRNASer.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-26-4

References:

1. Plapp, R. and Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. 18. Purification and properties of L-alanyl transfer ribonucleic acid-uridine diphosphate-N-acetylmuramyl-pentapeptide transferase from Lactobacillus viridescens. J. Biol. Chem. 245 (1970) 3675-3682. [PMID: 4248527]

[EC 2.3.2.10 created 1972, modified 2013]

EC 2.3.2.11

Accepted name: alanylphosphatidylglycerol synthase

Reaction: L-alanyl-tRNAAla + phosphatidylglycerol = tRNAAla + 3-O-L-alanyl-1-O-phosphatidylglycerol

Other name(s): O-alanylphosphatidylglycerol synthase; alanyl phosphatidylglycerol synthetase

Systematic name: L-alanyl-tRNAAla:phosphatidylglycerol alanyltransferase

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37257-27-5

References:

1. Gould, R.M., Thornton, M.P., Liepkalns, V. and Lennarz, W.J. Participation of aminoacyl transfer ribonucleic acid in aminoacyl phosphatidylglycerol synthesis. II. Specificity of alanyl phosphatidylglycerol synthetase. J. Biol. Chem. 243 (1968) 3096-3104. [PMID: 4297471]

[EC 2.3.2.11 created 1972, modified 2013]

EC 2.3.2.12

Accepted name: peptidyltransferase

Reaction: peptidyl-tRNA1 + aminoacyl-tRNA2 = tRNA1 + peptidyl(aminoacyl-tRNA2)

Other name(s): transpeptidase; ribosomal peptidyltransferase

Systematic name: peptidyl-tRNA:aminoacyl-tRNA N-peptidyltransferase

Comments: The enzyme is a ribozyme. Two non-equivlant ribonucleoprotein subunits operate in non-concerted fashion in peptide elongation. The small subunit forms the mRNA-binding machinery and decoding center, the large subunit performs the main ribosomal catalytic function in the peptidyl-transferase center.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9059-29-4

References:

1. Rychlik, I. Release of lysine peptides by puromycin from polylysyl-transfer ribonucleic acid in the presence of ribosomes. Biochim. Biophys. Acta 114 (1966) 425-427. [PMID: 5329275]

2. Rychlik, I., Cerná, J., Chládek, S., Zemlicka, J. and Haladová, Z. Substrate specificity of ribosomal peptidyl transferase: 2'(3')-O-aminoacyl nucleosides as acceptors of the peptide chain on the amino acid site. J. Mol. Biol. 43 (1969) 13-24. [PMID: 4897787]

3. Traut, R.R. and Monro, R.E. The puromycin reaction and its relation to protein synthesis. J. Mol. Biol. 10 (1964) 63-72.

4. Voorhees, R.M., Weixlbaumer, A., Loakes, D., Kelley, A.C. and Ramakrishnan, V. Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome. Nat. Struct. Mol. Biol. 16 (2009) 528-533. [PMID: 19363482]

[EC 2.3.2.12 created 1976]

EC 2.3.2.13

Accepted name: protein-glutamine γ-glutamyltransferase

Reaction: protein glutamine + alkylamine = protein N5-alkylglutamine + NH3

Other name(s): transglutaminase; Factor XIIIa; fibrinoligase; fibrin stabilizing factor; glutaminylpeptide γ-glutamyltransferase; polyamine transglutaminase; tissue transglutaminase; R-glutaminyl-peptide:amine γ-glutamyl transferase

Systematic name: protein-glutamine:amine γ-glutamyltransferase

Comments: Requires Ca2+. The γ-carboxamide groups of peptide-bound glutamine residues act as acyl donors, and the 6-amino-groups of protein- and peptide-bound lysine residues act as acceptors, to give intra- and inter-molecular N6-(5-glutamyl)-lysine crosslinks. Formed by proteolytic cleavage from plasma Factor XIII

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 80146-85-6

References:

1. Folk, J.E. and Chung, S.I. Molecular and catalytic properties of transglutaminases. Adv. Enzymol. Relat. Areas Mol. Biol. 38 (1973) 109-191. [PMID: 4151471]

2. Folk, J.E. and Cole, P.W. Mechanism of action of guinea pig liver transglutaminase. I. Purification and properties of the enzyme: identification of a functional cysteine essential for activity. J. Biol. Chem. 241 (1966) 5518-5525. [PMID: 5928192]

3. Folk, J.E. and Finlayson, J.S.The ε-γ-(glutamyl)lysine crosslink and the catalytic role of transglutaminases. Adv. Protein Chem. 31 (1977) 1-133. [PMID: 73346]

4. Takahashi, N., Takahashi, Y. and Putnam, F.W. Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta. Proc. Natl. Acad. Sci. USA 83 (1986) 8019-8023. [PMID: 2877456]

[EC 2.3.2.13 created 1978, modified 1981, modified 1983]

EC 2.3.2.14

Accepted name: D-alanine γ-glutamyltransferase

Reaction: L-glutamine + D-alanine = NH3 + γ-L-glutamyl-D-alanine

Systematic name: L-glutamine:D-alanine γ-glutamyltransferase

Comments: D-Phenylalanine and D-2-aminobutyrate can also act as acceptors, but more slowly. The enzyme also catalyses some of the reactions of EC 2.3.2.2 (γ-glutamyltransferase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9046-27-9

References:

1. Kawasaki, Y., Ogawa, T. and Sasaoka, K. Occurrence and some properties of a novel γ-glutamyltransferase responsible for the synthesis of γ-L-glutamyl-D-alanine in pea-seedlings. Biochim. Biophys. Acta 716 (1982) 194-200.

[EC 2.3.2.14 created 1989]

EC 2.3.2.15

Accepted name: glutathione γ-glutamylcysteinyltransferase

Reaction: glutathione + [Glu(-Cys)]n-Gly = Gly + [Glu(-Cys)]n+1-Gly

Other name(s): phytochelatin synthase; γ-glutamylcysteine dipeptidyl transpeptidase

Systematic name: glutathione:poly(4-glutamyl-cysteinyl)glycine 4-glutamylcysteinyltransferase

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 125390-02-5

References:

1. Grill, E., Löffler, S., Winnacker, E.-L. and Zenk, M.H. Phytochelatins, the heavy-metal-binding peptides of plants, are synthesized from glutathione by a specific γ-glutamylcysteine dipeptidyl transpeptidase (phytochelatin synthase). Proc. Natl. Acad. Sci. USA 86 (1989) 6838-6842.

[EC 2.3.2.15 created 1992]

EC 2.3.2.16

Accepted name: lipid II:glycine glycyltransferase

Reaction: MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + glycyl-tRNAGly = MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + tRNAGly

Other name(s): N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:N6-glycine transferase; femX (gene name); alanyl-D-alanine-diphospho-ditrans,octacis-undecaprenyl-N-acetylglucosamine:glycine N6-glycyltransferase

Systematic name: alanyl-D-alanine-diphospho-ditrans,octacis-undecaprenyl-N-acetylglucosamine:glycine N6-glycyltransferase

Comments: The enzyme from Staphylococcus aureus catalyses the transfer of glycine from a charged tRNA to MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphosphoundecaprenyl-GlcNAc (lipid II), attaching it to the N6 of the L-Lys at position 3 of the pentapeptide. This is the first step in the synthesis of the pentaglycine interpeptide bridge that is used in S. aureus for the crosslinking of different glycan strands to each other. Four additional Gly residues are subsequently attached by EC 2.3.2.17 (N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase) and EC 2.3.2.18 (N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-triglycine)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase).

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

References:

1. Schneider, T., Senn, M.M., Berger-Bachi, B., Tossi, A., Sahl, H.G. and Wiedemann, I. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol. Microbiol. 53 (2004) 675-685. [PMID: 15228543]

[EC 2.3.2.16 created 2010]

EC 2.3.2.17

Reaction: MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + 2 glycyl-tRNAGly = MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-tri-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + 2 tRNAGly

Other name(s): femA (gene name); N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-ditrans,octacis-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase

Systematic name: MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc:glycine glycyltransferase

Comments: This enzyme catalyses the successive transfer of two Gly moieties from charged tRNAs to MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc, attaching them to a Gly residue previously attached by EC 2.3.2.16 (lipid II:glycine glycyltransferase) to the N6 of the L-Lys at position 3 of the pentapeptide. This is the second step in the synthesis of the pentaglycine interpeptide bridge that is used by Staphylococcus aureus for the crosslinking of different glycan strands to each other. The next step is catalysed by EC 2.3.2.18 (N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-triglycine)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase). This enzyme is essential for methicillin resistance [1].

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

References:

1. Berger-Bachi, B., Barberis-Maino, L., Strassle, A. and Kayser, F.H. FemA, a host-mediated factor essential for methicillin resistance in Staphylococcus aureus: molecular cloning and characterization. Mol. Gen. Genet. 219 (1989) 263-269. [PMID: 2559314]

2. Johnson, S., Kruger, D. and Labischinski, H. FemA of Staphylococcus aureus: isolation and immunodetection. FEMS Microbiol. Lett. 132 (1995) 221-228. [PMID: 7590176]

3. Benson, T.E., Prince, D.B., Mutchler, V.T., Curry, K.A., Ho, A.M., Sarver, R.W., Hagadorn, J.C., Choi, G.H. and Garlick, R.L. X-ray crystal structure of Staphylococcus aureus FemA. Structure 10 (2002) 1107-1115. [PMID: 12176388]

4. Schneider, T., Senn, M.M., Berger-Bachi, B., Tossi, A., Sahl, H.G. and Wiedemann, I. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol. Microbiol. 53 (2004) 675-685. [PMID: 15228543]

[EC 2.3.2.17 created 2010]

EC 2.3.2.18

Accepted name: N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-triglycine)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase

Reaction: MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-tri-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + 2 glycyl-tRNAGly = MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-penta-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc + 2 tRNAGly

Other name(s): femB (gene name); N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-triglycine)-D-alanyl-D-alanine-ditrans,octacis-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase

Systematic name: MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-tri-Gly)-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenyl-GlcNAc:glycine glycyltransferasee

Comments: This Staphylococcus aureus enzyme catalyses the successive transfer of two Gly moieties from charged tRNAs to MurNAc-L-Ala-D-isoglutaminyl-L-Lys-(N6-tri-Gly)-D-Ala-D-Ala-diphosphoundecaprenyl-GlcNAc, attaching them to the three Gly molecules that were previously attached to the N6 of the L-Lys at position 3 of the pentapeptide by EC 2.3.2.16 (lipid II:glycine glycyltransferase) and EC 2.3.2.17 (N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase). This is the last step in the synthesis of the pentaglycine interpeptide bridge that is used in this organism for the crosslinking of different glycan strands to each other.

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

References:

1. Ehlert, K., Schroder, W. and Labischinski, H. Specificities of FemA and FemB for different glycine residues: FemB cannot substitute for FemA in staphylococcal peptidoglycan pentaglycine side chain formation. J. Bacteriol. 179 (1997) 7573-7576. [PMID: 9393725]

2. Rohrer, S. and Berger-Bachi, B. Application of a bacterial two-hybrid system for the analysis of protein-protein interactions between FemABX family proteins. Microbiology 149 (2003) 2733-2738. [PMID: 14523106]

3. Schneider, T., Senn, M.M., Berger-Bachi, B., Tossi, A., Sahl, H.G. and Wiedemann, I. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol. Microbiol. 53 (2004) 675-685. [PMID: 15228543]

[EC 2.3.2.18 created 2010]

EC 2.3.2.19

Accepted name: ribostamycin:4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase

Reaction: 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] + ribostamycin = γ-L-glutamyl-butirosin B + BtrI acyl-carrier protein

Other name(s): btrH (gene name)

Systematic name: ribostamycin:4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase

Comments: The enzyme attaches the side chain of the aminoglycoside antibiotics of the butirosin family. The side chain confers resistance against several aminoglycoside-modifying enzymes.

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

References:

1. Llewellyn, N.M., Li, Y. and Spencer, J.B. Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain. Chem. Biol. 14 (2007) 379-386. [PMID: 17462573]

[EC 2.3.2.19 created 2012]

EC 2.3.2.20

Accepted name: cyclo(L-leucyl-L-phenylalanyl) synthase

Reaction: L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe = tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)

For diagram of reaction click here.

Glossary: cyclo(L-leucyl-L-phenylalanyl) = (3S,6S)-3-benzyl-6-(2-methylpropyl)piperazine-2,5-dione

Other name(s): AlbC; cFL synthase

Systematic name: L-leucyl-tRNALeu:L-phenylalanyl-tRNAPhe leucyltransferase (cyclizing)

Comments: The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the L-phenylalanine residue [2]. The protein, found in the bacterium Streptomyces noursei, also forms cyclo(L-phenylalanyl-L-phenylalanyl), cyclo(L-methionyl-L-phenylalanyl), cyclo(L-phenylalanyl-L-tyrosyl) and cyclo(L-methionyl-L-tyrosyl) [1].

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

References:

1. Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414-420. [PMID: 19430487]

2. Sauguet, L., Moutiez, M., Li, Y., Belin, P., Seguin, J., Le Du, M.H., Thai, R., Masson, C., Fonvielle, M., Pernodet, J.L., Charbonnier, J.B. and Gondry, M. Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis. Nucleic Acids Res. 39 (2011) 4475-4489. [PMID: 21296757]

[EC 2.3.2.20 created 2013]

EC 2.3.2.21

Accepted name: cyclo(L-tyrosyl-L-tyrosyl) synthase

Reaction: 2 L-tyrosyl-tRNATyr = 2 tRNATyr + cyclo(L-tyrosyl-L-tyrosyl)

For diagram of reaction click here.

Glossary: cyclo(L-tyrosyl-L-tyrosyl) = (3S,6S)-3,6-bis[(4-hydroxyphenyl)methyl]piperazine-2,5-dione

Other name(s): Rv2275 (gene name); cYY synthase; cyclodityrosine synthase

Systematic name: L-tyrosyl-tRNATyr:L-tyrosyl-tRNATyr tyrosyltransferase (cyclizing)

Comments: The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-tyrosine residue [2]. The protein, from the bacterium Mycobacterium tuberculosis, also forms small amounts of cyclo(L-tyrosyl-L-phenylalanyl) [1].

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

References:

1. Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414-420. [PMID: 19430487]

2. Vetting, M.W., Hegde, S.S. and Blanchard, J.S. The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase. Nat. Chem. Biol. 6 (2010) 797-799. [PMID: 20852636]

[EC 2.3.2.21 created 2013]

EC 2.3.2.22

Accepted name: cyclo(L-leucyl-L-leucyl) synthase

Reaction: 2 L-leucyl-tRNALeu = 2 tRNALeu + cyclo(L-leucyl-L-leucyl)

For diagram of reaction click here.

Glossary: cyclo(L-leucyl-L-leucyl) = (3S,6S)-3,6-bis(2-methylpropyl)piperazine-2,5-dione

Other name(s): YvmC; cLL synthase; cyclodileucine synthase

Systematic name: L-leucyl-tRNALeu:L-leucyl-tRNALeu leucyltransferase (cyclizing)

Comments: The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-leucine residue [2]. The proteins from bacteria of the genus Bacillus also form small amounts of cyclo(L-phenylalanyl-L-leucyl) and cyclo(L-leucyl-L-methionyl) [1].

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

References:

1. Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414-420. [PMID: 19430487]

2. Bonnefond, L., Arai, T., Sakaguchi, Y., Suzuki, T., Ishitani, R. and Nureki, O. Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA synthetase paralog. Proc. Natl. Acad. Sci. USA 108 (2011) 3912-3917. [PMID: 21325056]

[EC 2.3.2.22 created 2013]

EC 2.3.2.23

Accepted name: E2 ubiquitin-conjugating enzyme

Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine

Other name(s): ubiquitin-carrier-protein E2; UBC (ambiguous); ubiquitin-conjugating enzyme E2

Systematic name: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:[E2 ubiquitin-conjugating enzyme] ubiquitinyl transferase

Comments: The E2 ubiquitin-conjugating enzyme acquires the activated ubquitin from the E1 ubiquitin-activating enzyme (EC 6.2.1.45) and binds it via a transthioesterification reaction to itself. In the human enzyme the catalytic center is located at Cys-87 where ubiquitin is bound via its C-terminal glycine in a thioester linkage.

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

References:

1. van Wijk, S.J. and Timmers, H.T. The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins. FASEB J. 24 (2010) 981-993. [PMID: 19940261]

2. David, Y., Ziv, T., Admon, A. and Navon, A. The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines. J. Biol. Chem. 285 (2010) 8595-8604. [PMID: 20061386]

3. Papaleo, E., Casiraghi, N., Arrigoni, A., Vanoni, M., Coccetti, P. and De Gioia, L. Loop 7 of E2 enzymes: an ancestral conserved functional motif involved in the E2-mediated steps of the ubiquitination cascade. PLoS One 7 (2012) e40786. [PMID: 22815819]

4. Cook, B.W. and Shaw, G.S. Architecture of the catalytic HPN motif is conserved in all E2 conjugating enzymes. Biochem. J. 445 (2012) 167-174. [PMID: 22563859]

5. Li, D.F., Feng, L., Hou, Y.J. and Liu, W. The expression, purification and crystallization of a ubiquitin-conjugating enzyme E2 from Agrocybe aegerita underscore the impact of His-tag location on recombinant protein properties. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69 (2013) 153-157. [PMID: 23385757]

[EC 2.3.2.23 created 2015]

EC 2.3.2.24

Accepted name: (E3-independent) E2 ubiquitin-conjugating enzyme

Reaction: [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N6-monoubiquitinyl-L-lysine (overall reaction)
(1a) [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [(E3-independent) E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + [(E3-independent) ubiquitin-conjugating enzyme]-S-monoubiquitinyl-L-cysteine
(1b) [(E3-independent) E2 ubiquitin-conjugating E2 enzyme]-S-monoubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [(E3-independent) E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-monoubiquitinyl-L-lysine

Other name(s): E2-230K; UBE2O; E3-independent ubiquitin-conjugating enzyme E2

Systematic name: [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine:L-lysine ubiquitinyl transferase ([E3 ubiquitin transferase]-independent)

Comments: The enzyme transfers a single ubiquitin directly from an ubiquitinated E1 ubiquitin-activating enzyme to itself, and on to a lysine residue of the acceptor protein without involvement of E3 ubiquitin transferases (cf. EC 2.3.2.26, EC 2.3.2.27). It forms a labile ubiquitin adduct in the presence of E1, ubiquitin, and Mg2+-ATP and catalyses the conjugation of ubiquitin to protein substrates, independently of E3. This transfer has only been observed with small proteins. In vitro a transfer to small acceptors (e.g. L-lysine, N-acetyl-L-lysine methyl ester) has been observed [1].

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

References:

1. Pickart, C.M. and Rose, I.A. Functional heterogeneity of ubiquitin carrier proteins. J. Biol. Chem. 260 (1985) 1573-1581. [PMID: 2981864]

2. Hoeller, D., Hecker, C.M., Wagner, S., Rogov, V., Dotsch, V. and Dikic, I. E3-independent monoubiquitination of ubiquitin-binding proteins. Mol. Cell 26 (2007) 891-898. [PMID: 17588522]

3. Ramanathan, H.N., Zhang, G. and Ye, Y. Monoubiquitination of EEA1 regulates endosome fusion and trafficking. Cell Biosci 3 (2013) 24. [PMID: 23701900]

[EC 2.3.2.24 created 2015]

EC 2.3.2.25

Accepted name: N-terminal E2 ubiquitin-conjugating enzyme

Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid = [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein] (overall reaction)
(1a) S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [N-terminal E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[N-terminal ubiquitin-conjugating enzyme]-L-cysteine
(1b) S-ubiquitinyl-[N-terminal E2 ubiquitin-conjugating E2 enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid = [N-terminal E2 ubiquitin-conjugating enzyme]-L-cysteine + N-ubiquitinyl-[acceptor protein]-N-terminal amino acid

Other name(s): Ube2w; N-terminal ubiquitin-conjugating enzyme E2

Systematic name: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:acceptor protein ubiquitin ligase (peptide bond-forming)

Comments: The enzyme ubiquitinylates the N-terminus of the acceptor protein. It is not reactive towards free lysine.

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

References:

1. Breitschopf, K., Bengal, E., Ziv, T., Admon, A. and Ciechanover, A. A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein. EMBO J. 17 (1998) 5964-5973. [PMID: 9774340]

2. Tatham, M.H., Plechanovova, A., Jaffray, E.G., Salmen, H. and Hay, R.T. Ube2W conjugates ubiquitin to α-amino groups of protein N-termini. Biochem. J. 453 (2013) 137-145. [PMID: 23560854]

3. Scaglione, K.M., Basrur, V., Ashraf, N.S., Konen, J.R., Elenitoba-Johnson, K.S., Todi, S.V. and Paulson, H.L. The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. J. Biol. Chem. 288 (2013) 18784-18788. [PMID: 23696636]

[EC 2.3.2.25 created 2015]

EC 2.3.2.26

Accepted name: HECT-type E3 ubiquitin transferase

Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine (overall reaction)
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [HECT-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [HECT-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine

Glossary: HECT protein domain = Homologous to the E6-AP Carboxyl Terminus protein domain

Other name(s): HECT E3 ligase (misleading); ubiquitin transferase HECT-E3; S-ubiquitinyl-[HECT-type E3-ubiquitin transferase]-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming)

Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming)

Comments: In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ε-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.

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

References:

1. Maspero, E., Mari, S., Valentini, E., Musacchio, A., Fish, A., Pasqualato, S. and Polo, S. Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation. EMBO Rep. 12 (2011) 342-349. [PMID: 21399620]

2. Metzger, M.B., Hristova, V.A. and Weissman, A.M. HECT and RING finger families of E3 ubiquitin ligases at a glance. J. Cell Sci. 125 (2012) 531-537. [PMID: 22389392]

[EC 2.3.2.26 created 2015, modified 2017]

EC 2.3.2.27

Accepted name: RING-type E3 ubiquitin transferase

Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine

Glossary: RING = Really Interesting New Gene

Other name(s): RING E3 ligase (misleading); ubiquitin transferase RING E3; S-ubiquitinyl-[ubiquitin-conjugating E2 enzyme]-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming, RING-type)

Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)

Comments: RING E3 ubiquitin transferases serve as mediators bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) and an acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ε-amino group of an L-lysine residue of the acceptor protein. Unlike EC 2.3.2.26, HECT-type E3 ubiquitin transferase, the RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin. Many members of the RING-type E3 ubiquitin transferase family are not able to bind a substrate directly, and form a complex with a cullin scaffold protein and a substrate recognition module (the complexes are named CRL for Cullin-RING-Ligase). In these complexes, the RING-type E3 ubiquitin transferase provides an additional function, mediating the transfer of a NEDD8 protein from a dedicated E2 carrier to the cullin protein (see EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase). cf. EC 2.3.2.31, RBR-type E3 ubiquitin transferase.

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

References:

1. Eisele, F. and Wolf, D.H. Degradation of misfolded protein in the cytoplasm is mediated by the ubiquitin ligase Ubr1. FEBS Lett. 582 (2008) 4143-4146. [PMID: 19041308]

2. Metzger, M.B., Hristova, V.A. and Weissman, A.M. HECT and RING finger families of E3 ubiquitin ligases at a glance. J. Cell Sci. 125 (2012) 531-537. [PMID: 22389392]

3. Plechanovova, A., Jaffray, E.G., Tatham, M.H., Naismith, J.H. and Hay, R.T. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature 489 (2012) 115-120. [PMID: 22842904]

4. Pruneda, J.N., Littlefield, P.J., Soss, S.E., Nordquist, K.A., Chazin, W.J., Brzovic, P.S. and Klevit, R.E. Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases. Mol. Cell 47 (2012) 933-942. [PMID: 22885007]

5. Metzger, M.B., Pruneda, J.N., Klevit, R.E. and Weissman, A.M. RING -type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim. Biophys. Acta 1843 (2014) 47-60. [PMID: 23747565]

[EC 2.3.2.27 created 2015, modified 2017]

EC 2.3.2.28

Accepted name: L-allo-isoleucyltransferase

Reaction: L-allo-isoleucyl-S-[CmaA peptidyl-carrier protein] + holo-[CmaD peptidyl-carrier protein] = L-allo-isoleucyl-S-[CmaD peptidyl-carrier protein] + holo-[CmaA peptidyl-carrier protein]

Glossary: L-allo-isoleucine = (2S,3R)-2-amino-3-methylpentanoic acid

Other name(s): CmaE

Systematic name: L-allo-isoleucyl-S-[CmaA peptidyl-carrier protein]:holo-[CmaD peptidyl-carrier protein] L-allo-isoleucyltransferase

Comments: The enzyme, characterized from the bacterium Pseudomonas syringae, is involved in the biosynthesis of the toxin coronatine.

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

References:

1. Vaillancourt, F.H., Yeh, E., Vosburg, D.A., O'Connor, S.E. and Walsh, C.T. Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis. Nature 436 (2005) 1191-1194. [PMID: 16121186]

2. Strieter, E.R., Vaillancourt, F.H. and Walsh, C.T. CmaE: a transferase shuttling aminoacyl groups between carrier protein domains in the coronamic acid biosynthetic pathway. Biochemistry 46 (2007) 7549-7557. [PMID: 17530782]

[EC 2.3.2.28 created 2015]

EC 2.3.2.29

Accepted name: aspartate/glutamate leucyltransferase

Reaction: (1) L-leucyl-tRNALeu + N-terminal L-glutamyl-[protein] = tRNALeu + N-terminal L-leucyl-L-glutamyl-[protein]
(2) L-leucyl-tRNALeu + N-terminal L-aspartyl-[protein] = tRNALeu + N-terminal L-leucyl-L-aspartyl-[protein]

Other name(s): leucylD,E-transferase; bpt (gene name)

Systematic name: L-leucyl-tRNALeu:[protein] N-terminal L-glutamate/L-aspartate leucyltransferase

Comments: The enzyme participates in the N-end rule protein degradation pathway in certain bacteria, by attaching the primary destabilizing residue L-leucine to the N-termini of proteins that have an N-terminal L-aspartate or L-glutamate residue. Once modified, the proteins are recognized by EC 3.4.21.92, the ClpAP/ClpS endopeptidase system. cf. EC 2.3.2.6, lysine/arginine leucyltransferase, and EC 2.3.2.8, arginyltransferase.

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

References:

1. Graciet, E., Hu, R.G., Piatkov, K., Rhee, J.H., Schwarz, E.M. and Varshavsky, A. Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen. Proc. Natl. Acad. Sci. USA 103 (2006) 3078-3083. [PMID: 16492767]

[EC 2.3.2.29 created 2016]

EC 2.3.2.30

Accepted name: L-ornithine Nα-acyltransferase

Reaction: L-ornithine + a (3R)-3-hydroxyacyl-[acyl-carrier protein] = a lyso-ornithine lipid + a holo-[acyl-carrier protein]

Glossary: a lyso-ornithine lipid = an Nα-[(3R)-hydroxy-acyl]-L-ornithine

Other name(s): olsB (gene name)

Systematic name: L-ornithine Nα-(3R)-3-hydroxy-acyltransferase

Comments: The enzyme, found in bacteria, catalyses the first step in the biosynthesis of ornithine lipids.

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

References:

1. Gao, J.L., Weissenmayer, B., Taylor, A.M., Thomas-Oates, J., Lopez-Lara, I.M. and Geiger, O. Identification of a gene required for the formation of lyso-ornithine lipid, an intermediate in the biosynthesis of ornithine-containing lipids. Mol. Microbiol. 53 (2004) 1757-1770. [PMID: 15341653]

2. Vences-Guzman, M.A., Guan, Z., Bermudez-Barrientos, J.R., Geiger, O. and Sohlenkamp, C. Agrobacteria lacking ornithine lipids induce more rapid tumour formation. Environ Microbiol 15 (2013) 895-906. [PMID: 22958119]

[EC 2.3.2.30 created 2017]

EC 2.3.2.31

Accepted name: RBR-type E3 ubiquitin transferase

Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine (overall reaction)
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RBR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [RBR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine

Glossary: RBR = RING between RING
RING = Really Interesting New Gene

Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RBR-type)

Comments: RBR-type E3 ubiquitin transferases have two RING fingers separated by an internal motif (IBR, for In Between RING). The enzyme interacts with the CRL (Cullin-RING ubiquitin Ligase) complexes formed by certain RING-type E3 ubiquitin transferase (see EC 2.3.2.27), which include a neddylated cullin scaffold protein and a substrate recognition module. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue in the RING2 domain, followed by the transfer of the ubiquitin from RING2 to the substrate [4]. Once the substrate has been ubiquitylated by the RBR-type ligase, it can be ubiqutylated further using ubiquitin carried directly on E2 enzymes, in a reaction catalysed by EC 2.3.2.27. Activity of the RBR-type enzyme is dependent on neddylation of the cullin protein in the CRL complex [2,4]. cf. EC 2.3.2.26, HECT-type E3 ubiquitin transferase, EC 2.3.2.27, RING-type E3 ubiquitin transferase, and EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase.

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

References:

1. Wenzel, D.M., Lissounov, A., Brzovic, P.S. and Klevit, R.E. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474 (2011) 105-108. [PMID: 21532592]

2. Kelsall, I.R., Duda, D.M., Olszewski, J.L., Hofmann, K., Knebel, A., Langevin, F., Wood, N., Wightman, M., Schulman, B.A. and Alpi, A.F. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 32 (2013) 2848-2860. [PMID: 24076655]

3. Duda, D.M., Olszewski, J.L., Schuermann, J.P., Kurinov, I., Miller, D.J., Nourse, A., Alpi, A.F. and Schulman, B.A. Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism. Structure 21 (2013) 1030-1041. [PMID: 23707686]

4. Scott, D.C., Rhee, D.Y., Duda, D.M., Kelsall, I.R., Olszewski, J.L., Paulo, J.A., de Jong, A., Ovaa, H., Alpi, A.F., Harper, J.W. and Schulman, B.A. Two distinct types of E3 ligases work in unison to regulate substrate ubiquitylation. Cell 166 (2016) 1198-1214.e24. [PMID: 27565346]

[EC 2.3.2.31 created 2017]

EC 2.3.2.32

Accepted name: cullin-RING-type E3 NEDD8 transferase

Reaction: S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N6-[NEDD8-protein]-yl-[cullin]-L-lysine

Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein

Other name(s): RBX1 (gene name)

Systematic name: S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine:cullin [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)

Comments: Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form a complex with a cullin scaffold protein and a substrate recognition module, which is named CRL for Cullin-RING-Ligase. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. The transfer of NEDD8 from a NEDD8-specific E2 enzyme onto the cullin protein is a secondary function of the RING-type E3 ubiquitin transferase in the CRL complex. The process requires auxiliary factors that belong to the DCN1 (defective in cullin neddylation 1) family.

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

References:

1. Kim, A.Y., Bommelje, C.C., Lee, B.E., Yonekawa, Y., Choi, L., Morris, L.G., Huang, G., Kaufman, A., Ryan, R.J., Hao, B., Ramanathan, Y. and Singh, B. SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation. J. Biol. Chem. 283 (2008) 33211-33220. [PMID: 18826954]

2. Kurz, T., Chou, Y.C., Willems, A.R., Meyer-Schaller, N., Hecht, M.L., Tyers, M., Peter, M. and Sicheri, F. Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Mol. Cell 29 (2008) 23-35. [PMID: 18206966]

3. Scott, D.C., Monda, J.K., Grace, C.R., Duda, D.M., Kriwacki, R.W., Kurz, T. and Schulman, B.A. A dual E3 mechanism for Rub1 ligation to Cdc53. Mol. Cell 39 (2010) 784-796. [PMID: 20832729]

4. Scott, D.C., Sviderskiy, V.O., Monda, J.K., Lydeard, J.R., Cho, S.E., Harper, J.W. and Schulman, B.A. Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8. Cell 157 (2014) 1671-1684. [PMID: 24949976]

5. Monda, J.K., Scott, D.C., Miller, D.J., Lydeard, J., King, D., Harper, J.W., Bennett, E.J. and Schulman, B.A. Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes. Structure 21 (2013) 42-53. [PMID: 23201271]

[EC 2.3.2.32 created 2017]


Continued with EC 2.3.3
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