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]
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]
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 2.3.2.4 Transferred entry: γ-glutamylcyclotransferase. Now classified as EC 4.3.2.9, γ-glutamylcyclotransferase (EC 2.3.2.4 created 1972, deleted 2017)]
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.
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]
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.
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 2-sulfanylethan-1-ol (2-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, PDB, 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]
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.
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, PDB, 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]
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, PDB, 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]
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]
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]
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.
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, PDB, 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.
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, PDB, 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]
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]
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]
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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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, PDB, 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]
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]
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]
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]
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, PDB, 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]
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, PDB, 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]
Accepted name: RCR-type E3 ubiquitin transferase
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine (overall reaction)
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RCR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [RCR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine
Glossary: RCR = RING-Cys-Relay
RING = Really Interesting New Gene
Other name(s): MYCBP2; PHR1
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RCR-type)
Comments: RCR-type E3 ubiquitin transferases is a class of RING-type E3 ubiquitin transferase (see EC 2.3.2.27) that mediates ubiquitylation of acceptor proteins via an internal cysteine residue. 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 on a mediator loop of the RCR-type ligase. The ubiquitin may be transferred to a second internal cysteine before the transfer of the ubiquitin from the RCR-type ligase to the substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Pao, K.C., Wood, N.T., Knebel, A., Rafie, K., Stanley, M., Mabbitt, P.D., Sundaramoorthy, R., Hofmann, K., van Aalten, D.MF. and Virdee, S. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature 556 (2018) 381-385. [PMID: 29643511]
Accepted name: E2 NEDD8-conjugating enzyme
Reaction: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): NEDD8-carrier-protein E2; NEDD8-conjugating enzyme E2; UBE2M (gene name); UBE2F (gene name)
Systematic name: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine:[E2 NEDD8-conjugating enzyme] [NEDD8-protein]-yl transferase
Comments: Some RING-type E3 ubiquitin transferases (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. EC 6.2.1.64, E1 NEDD8-activating enzyme, activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of an E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263-2268. [PMID: 9694792]
2. Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036-12042. [PMID: 10207026]
3. Huang, D.T., Miller, D.W., Mathew, R., Cassell, R., Holton, J.M., Roussel, M.F. and Schulman, B.A. A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat. Struct. Mol. Biol. 11 (2004) 927-935. [PMID: 15361859]
4. Huang, D.T., Ayrault, O., Hunt, H.W., Taherbhoy, A.M., Duda, D.M., Scott, D.C., Borg, L.A., Neale, G., Murray, P.J., Roussel, M.F. and Schulman, B.A. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33 (2009) 483-495. [PMID: 19250909]
Accepted name: capsaicin synthase
Reaction: (6E)-8-methylnon-6-enoyl-CoA + vanillylamine = CoA + capsaicin
Other name(s): CS (gene name) (ambiguous); Pun1 (locus name)
Systematic name: (6E)-8-methylnon-6-enoyl-CoA:vanillylamine 8-methylnon-6-enoyltransferase
Comments: The enzyme, found only in plants that belong to the Capsicum genus, catalyses the last step in the biosynthesis of capsaicinoids. The enzyme catalyses the acylation of vanillylamine by a branched-chain fatty acid. The exact structure of the fatty acid determines the type of capsaicinoid formed.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Blum, E., Liu, K., Mazourek, M., Yoo, E.Y., Jahn, M. and Paran, I. Molecular mapping of the C locus for presence of pungency in Capsicum. Genome 45 (2002) 702-705. [PMID: 12175073]
2. Stewart, C., Jr., Kang, B.C., Liu, K., Mazourek, M., Moore, S.L., Yoo, E.Y., Kim, B.D., Paran, I. and Jahn, M.M. The Pun1 gene for pungency in pepper encodes a putative acyltransferase. Plant J. 42 (2005) 675-688. [PMID: 15918882]
3. Kim, S., Park, M., Yeom, S.I., Kim, Y.M., Lee, J.M., Lee, H.A., Seo, E., Choi, J., Cheong, K., Kim, K.T., Jung, K., Lee, G.W., Oh, S.K., Bae, C., Kim, S.B., Lee, H.Y., Kim, S.Y., Kim, M.S., Kang, B.C., Jo, Y.D., Yang, H.B., Jeong, H.J., Kang, W.H., Kwon, J.K., Shin, C., Lim, J.Y., Park, J.H., Huh, J.H., Kim, J.S., Kim, B.D., Cohen, O., Paran, I., Suh, M.C., Lee, S.B., Kim, Y.K., Shin, Y., Noh, S.J., Park, J., Seo, Y.S., Kwon, S.Y., Kim, H.A., Park, J.M., Kim, H.J., Choi, S.B., Bosland, P.W., Reeves, G., Jo, S.H., Lee, B.W., Cho, H.T., Choi, H.S., Lee, M.S., Yu, Y., Do Choi, Y., Park, B.S., van Deynze, A., Ashrafi, H., Hill, T., Kim, W.T., Pai, H.S., Ahn, H.K., Yeam, I., Giovannoni, J.J., Rose, J.K., Sorensen, I., Lee, S.J., Kim, R.W., Choi, I.Y., Choi, B.S., Lim, J.S., Lee, Y.H. and Choi, D. Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species. Nat. Genet. 46 (2014) 270-278. [PMID: 24441736]
Accepted name: RING-type E3 ubiquitin transferase (cysteine targeting)
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine
Glossary: RING = Really Interesting New Gene
Other name(s): RING E3 ligase (misleading)
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (thioester bond-froming; RING-type)
Comments: This relatively rare subpopulation of RING-type E3 ubiquitin transferases (cf. EC 2.3.2.27), found in mammals and herpes viruses, can transfer ubiquitin to a cysteine residue in target proteins. Additional ubiquitin molecules are polymerized on top of the initial ubiquitin molecule by formation of an isopeptide linkage with lysine48 in the pre-attached ubiquitin [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, PDB, CAS registry number:
References:
1. Cadwell, K. and Coscoy, L. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science 309 (2005) 127-130. [PMID: 15994556]
2. Wang, Y.J., Bian, Y., Luo, J., Lu, M., Xiong, Y., Guo, S.Y., Yin, H.Y., Lin, X., Li, Q., Chang, C.CY., Chang, T.Y., Li, B.L. and Song, B.L. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation. Nat. Cell Biol. 19 (2017) 808-819. [PMID: 28604676]
3. Zhou, Z.S., Li, M.X., Liu, J., Jiao, H., Xia, J.M., Shi, X.J., Zhao, H., Chu, L., Liu, J., Qi, W., Luo, J. and Song, B.L. Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. Nat. Commun. 11 (2020) 379. [PMID: 31953408]
Accepted name: ergosteryl-3β-O-L-aspartate synthase
Reaction: L-aspartyl-tRNAAsp + ergosterol = tRNAAsp + 1-(ergostan-3β-yl)-L-aspartate
Other name(s): ErdS
Systematic name: L-aspartyl-tRNAAsp:ergosterol-3β-O-L-aspartyltransferase
Comments: The enzyme, detected in fungal species that belong to the Ascomycota and Basidiomycota phyla and characterized from Aspergillus fumigatus, is bifunctional. The AspRS domain catalyses the transfer of L-aspartate to tRNAAsp (EC 6.1.1.12), while the second domain carries out the transfer of L-aspartate to the 3β-hydroxyl of ergosterol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Yakobov, N., Fischer, F., Mahmoudi, N., Saga, Y., Grube, C.D., Roy, H., Senger, B., Grob, G., Tatematsu, S., Yokokawa, D., Mouyna, I., Latge, J.P., Nakajima, H., Kushiro, T. and Becker, H.D. RNA-dependent sterol aspartylation in fungi. Proc. Natl. Acad. Sci. USA 117 (2020) 14948-14957. [PMID: 32541034]