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Information on EC 2.3.2.2 - gamma-glutamyltransferase and Organism(s) Escherichia coli and UniProt Accession P18956
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2.3.2.2 gamma-glutamyltransferaseIUBMB 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].
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- 2.3.2.2
- aminotransferase
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alt
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- cholesterol
- albumin
- triglyceride
- bile
- biliary
- women
- creatinine
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- transaminase
- hepatocytes
- cirrhosis
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- duct
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uric
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c-reactive
- steatosis
- aminopeptidase
- jaundice
-
drinkers
-
hepatotoxicity
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non-alcoholic
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intrahepatic
- nafld
-
nephrotoxicity
-
ursodeoxycholic
-
waist
-
ultrasonography
- diethylnitrosamine
-
circumference
-
corpuscular
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hepatocarcinogenesis
-
abuse
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hepatectomy
- hepatobiliary
- phenobarbital
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preneoplastic
- alpha-fetoprotein
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homa-ir
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abstinence
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n-acetyl-beta-d-glucosaminidase
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cholangiopancreatography
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elastography
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- synthesis
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
a (5-L-glutamyl)-peptide
+
=
+
Synonyms
ggt, gamma-glutamyl transpeptidase, gamma-glutamyltransferase, gamma-glutamyltranspeptidase, gamma-gtp, gamma glutamyl transferase, glutamyl transpeptidase, gamma-glutamyl-transpeptidase, gammagt, blggt, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-glutamyl transpeptidase
-
-
-
-
gamma-glutamyl peptidyltransferase
-
-
-
-
gamma-glutamyl transpeptidase
gamma-GPT
-
-
-
-
gamma-GT
-
-
-
-
gamma-GTP
-
-
-
-
glutamyl transpeptidase
-
-
-
-
glutamyltransferase, gamma-
-
-
-
-
L-gamma-glutamyl transpeptidase
-
-
-
-
L-gamma-glutamyltransferase
-
-
-
-
L-glutamyltransferase
-
-
-
-
gamma-glutamyl transpeptidase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid
the Escherichia coli enzyme is a nonselective enzyme that accommodates substrates without specifically recognizing the C-terminal carboxy group of the Cys-Gly moiety of gamma-glutamyl compounds or the acceptor molecules
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aminoacyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(5-L-glutamyl)-peptide:amino-acid 5-glutamyltransferase
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].
CAS REGISTRY NUMBER
COMMENTARY
9046-27-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a (5-L-glutamyl)-peptide + an amino acid
a peptide + a 5-L-glutamyl amino acid
-
-
-
?
L-glutamylhydrazine + methylamine
gamma-L-glutamylmethylamide + hydrazine
recombinant enzyme, method optimmization and evaluation, overview
-
-
?
5-D-glutamyl-4-nitroanilide + acceptor
4-nitroaniline + 5-D-glutamyl-acceptor
-
-
-
-
?
5-L-glutamyl-4-nitroanilide + ethylamine
theanine + 4-nitroaniline
-
-
-
-
?
5-L-glutamyl-4-nitroanilide + glycylglycine
4-nitroaniline + 5-L-glutamylglycylglycine
-
-
-
-
?
5-L-glutamyl-4-nitroanilide + L-asparagine
4-nitroaniline + 5-L-glutamyl-L-asparagine
-
-
-
-
?
5-L-glutamyl-4-nitroanilide + L-cystine
4-nitroaniline + 5-L-glutamyl-L-cystine
-
-
-
-
?
7-(N-gamma-glutamylamino)-4-methylcoumarin + H2O
7-amino-4-methylcoumarin + ?
-
-
-
-
?
D-Gln + Ala
D-Glu-Ala + NH3
-
6.2% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Cys
D-Glu-Cys + NH3
-
19.3% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Glu
D-Glu-Glu + NH3
-
8.1% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Gly
D-Glu-Gly + NH3
-
20.1% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + His
D-Glu-His + NH3
-
116% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + L-Val
D-Glu-Val + NH3
-
8.1% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Met
D-Glu-Met + NH3
-
352% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Phe
D-Glu-Phe + NH3
-
144% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + taurine
D-Glu-taurine + NH3
-
422% of the activity with D-Gln and Gly-Gly
-
-
?
D-Gln + Trp
D-Glu-Trp + NH3
-
558% of the activity with D-Gln and Gly-Gly
-
-
?
glutathione + acceptor
cysteinylglycine + 5-L-glutamyl-acceptor
-
acceptor: amino acids
-
-
?
L-Glu-4-nitroanilide + glutathione
4-nitroaniline + 5-L-glutamyl-glutathione
-
-
-
-
?
5-L-glutamyl-4-nitroanilide + Gly-Gly
4-nitroaniline + 5-L-glutamyl-Gly-Gly
-
-
-
?
5-L-glutamyl-4-nitroanilide + Gly-Gly
4-nitroaniline + 5-L-glutamyl-Gly-Gly
-
-
-
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
concurrent reaction: hydrolase reaction with H2O as acceptor
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
concurrent reaction: hydrolase reaction with H2O as acceptor
-
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
Glu-donor is 5-L-Glu-4-nitroanilide
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
acceptors are amino acids or dipeptides
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
isozyme A prefers basic and aromatic amino acids as acceptors
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
concurrent reaction: autotranspeptidation with another donor molecule as acceptor
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
concurrent reaction: autotranspeptidation with another donor molecule as acceptor
-
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
Glu-donor is GSH
-
?
(5-L-glutamyl)-peptide + acceptor + H+
peptide + 5-L-glutamyl amino acid
-
donor specificity, overview
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a (5-L-glutamyl)-peptide + an amino acid
a peptide + a 5-L-glutamyl amino acid
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-amino-4-([3-(carboxymethyl)phenoxy](methoyl)phosphoryl)butanoic acid
i.e. GGsTop, weak inhibition, structure-activity relationship, Escherichia coli enzyme GGT in complex with the inhibitor, Lys562 is the probable residue for the recognition of negative charge at C-terminal of GGsTop
2-amino 4-[4-chlorophenyl(methyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 610/per mol * s
2-amino 4-[methyl(phenyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 120/per mol * s
2-amino-4-[(4-methoxyphenyl)(methyl)phosphono]-butanoic acid
-
second-order rate constant for enzyme inactivation is 19/per mol * s
2-amino-4-[1-[N-(carboxymethyl)carbamoyl]propyl(phenyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 80/per mol * s
2-amino-4-[4-cyanophenyl(methyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 12000/per mol * s
2-amino-4-[methyl(4-methylphenyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 24/per mol * s
2-amino-4-[methyl(4-methylumbelliferyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 16000/per mol * s
2-amino-4-[methyl(4-nitrophenyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 35000/per mol * s
2-amino-4-[methyl(4-trifluoromethylphenyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 2900/per mol * s
2-amino-4-[[3-(carboxymethyl)phenyl](methyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 150/per mol * s
2-amino-4-[[4-(carboxymethyl)phenyl](methyl)phosphono]butanoic acid
-
second-order rate constant for enzyme inactivation is 210/per mol * s
L-(alphaS,5S)-alpha-Amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid
-
i.e. AT-125
L-(alphaS,5S)-alpha-Amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid
-
strong, irreversible, 1 mM
additional information
no inhibition of recombinant enzyme by 200 mM L-glutamylhydrazine
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
inhibition kinetics, overview
-
additional information
additional information
-
inhibition kinetics, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.8
truncation mutant lacking 17 amino acids at the N-terminus, pH 9.0, 40°C
4.9
truncation mutant lacking 11 amino acids at the N-terminus, pH 9.0, 40°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 12
activity range, over 60% of maximal activity at pH 7.5-10.5, profile overview
7 - 11
-
about 35% activity at pH 7.0, about 55% activity at pH 8.0, about 85% activity at pH 9.0, 100% acitivity at pH 10.0, about 75% activity at pH 11.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35 - 55
-
about 70% activity at 35°C, about 80% activity at 40°C, 100% activity at 45°C, about 85% activity at 50°C, about 45% activity at 55°C
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, hanging-drop vapor diffusion method, crystal structure of gamma-glutamyltransferase at 1.95 A resolution and structure of the gamma-glutamyl-enzyme intermediate trapped by flash cooling the GGT crystal soaked in glutathione solution and the structure of GGT in complex with L-glutamate
ammonium sulfate precipitation, hanging-drop vapor diffusion method, crystal structure of the T391A mutant gamma-glutamyltranspeptidase that lacks autocatalytic processing ability refined at 2.55 A resolution
in complex with azaserine and acivicin, at 1.65 A resolution. Both inhibitors bind to the substrate-binding pocketand form a covalent bond with the Ogamma atom of residue T391. The two amido nitrogen atoms of Gly483 and Gly484, which form the oxyanion hole, interact with the inhibitors directly or via a water molecule. In the azaserine complex the carbon atom that forms a covalent bond with Thr391 is sp3-hybridized
ammonium sulfate precipitation from 20 mM Tris-HCl, pH 8.0, 14.2 mg/ml protein, refrigerator, 1 week
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S463D
complete loss of activity, impaired autoproteolytic processing, increase in the critical bond distance of residues Q390-T391
S463K
complete loss of activity, impaired autoproteolytic processing, increase in the critical bond distance of residues Q390-T391
T391A
mutant protein without intramolecular autocatalytic processing activity
D433N
-
mutation enables gamma-glutamyltranspeptidase to deacylate glutaryl-7-aminocepha-losporanic acid, producing 7-aminocephalosporanic acid, which is a starting material for the synthesis of semisynthetic cephalosporins
additional information
additional information
construction of truncation mutants lacking 11, 17, 18, 20 and 26 amino acids at the N-terminus. Mutants lacking 11 and 17 amino acids show about 10% reduction in specific activity, mutants lacking 18 or more amino acids show a complete loss of activity
additional information
-
construction of truncation mutants lacking 11, 17, 18, 20 and 26 amino acids at the N-terminus. Mutants lacking 11 and 17 amino acids show about 10% reduction in specific activity, mutants lacking 18 or more amino acids show a complete loss of activity
additional information
immobilization of recombinant enzyme on 3% sodium alginates inpresence of 2% CaCl2, immobilized recombinant gamma-glutamyltranspeptidase cells exhibit favourable operational stability for enzymatic synthesis of gamma-glutamylmethylamide from L-glutamylhydrazine and methylamine, usage of L-glutamylhydrazine as an economical substrate, immobilized gamma-glutamyltranspeptidase cells are used for 10 reaction cycles, and the average conversion ratio from L-glutamylhydrazine to gamma-glutamylmethylamide reaches 93.2%. No inhibition by 200 mM L-glutamylhydrazine
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a truncated Escherichia coli Novablue gamma-glutamyltranspeptidase gene lacking the first 48-bp coding sequence for part of the signal sequence is amplified by polymerase chain reaction and cloned into expression vector pQE-30 to generate pQE-EcGGT. The maximum production of His6-tagged enzyme by Escherichia coli M15 is achieved with 0.1 mM IPTG induction for 12 h at 20°C
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
synthesis of theanine from 5-L-glutamyl-4-nitroanilide and ethylamine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Suzuki, H.; Kumagai, H.; Tochikura, T.
gamma-Glutamyltranspeptidase from Escherichia coli K-12: purification and properties
J. Bacteriol.
168
1325-1331
1986
Escherichia coli
Suzuki, H.; Kumagai, H.; Tochikura, T.
gamma-Glutamyltranspeptidase from Escherichia coli K-12: formation and localization
J. Bacteriol.
168
1332-1335
1986
Escherichia coli
Suzuki, H.; Izuka, S.; Minami, H.; Miyakawa, N.; Ishihara, S.; Kumagai, H.
Use of bacterial gamma-glutamyltranspeptidase for enzymatic synthesis of gamma-D-glutamyl compounds
Appl. Environ. Microbiol.
69
6399-6404
2003
Escherichia coli
Suzuki, H.; Miwa, C.; Ishihara, S.; Kumagai, H.
A single amino acid substitution converts gamma-glutamyltranspeptidase to a class IV cephalosporin acylase (glutaryl-7-aminocephalosporanic acid acylase)
Appl. Environ. Microbiol.
70
6324-6328
2004
Escherichia coli
Okada, T.; Suzuki, H.; Wada, K.; Kumagai, H.; Fukuyama, K.
Crystal structure of the gamma-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism
J. Biol. Chem.
282
2433-2439
2007
Escherichia coli (P18956), Escherichia coli
Okada, T.; Suzuki, H.; Wada, K.; Kumagai, H.; Fukuyama, K.
Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate
Proc. Natl. Acad. Sci. USA
103
6471-6476
2006
Escherichia coli (P18956), Escherichia coli
Yao, Y.F.; Weng, Y.M.; Hu, H.Y.; Ku, K.L.; Lin, L.L.
Expression optimization and biochemical characterization of a recombinant gamma-glutamyltranspeptidase from Escherichia coli novablue
Protein J.
25
431-441
2006
Escherichia coli, Escherichia coli Novablue
Han, L.; Hiratake, J.; Kamiyama, A.; Sakata, K.
Design, synthesis, and evaluation of gamma-phosphono diester analogues of glutamate as highly potent inhibitors and active site probes of gamma-glutamyl transpeptidase
Biochemistry
46
1432-1447
2007
Escherichia coli, Homo sapiens
Hsu, W.H.; Ong, P.L.; Chen, S.C.; Lin, L.L.
Contribution of Ser463 residue to the enzymatic and autoprocessing activities of Escherichia coli gamma-glutamyltranspeptidase
Indian J. Biochem. Biophys.
46
281-288
2009
Escherichia coli (P18956), Escherichia coli
Lo, H.F.; Chou, W.M.; Chen, P.J.; Lin, L.L.
Influence of signal-peptide truncations on the functional expression of Escherichia coli gamma -glutamyltranspeptidase
J. Basic Microbiol.
48
260-268
2008
Escherichia coli (P18956), Escherichia coli
Wada, K.; Hiratake, J.; Irie, M.; Okada, T.; Yamada, C.; Kumagai, H.; Suzuki, H.; Fukuyama, K.
Crystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists
J. Mol. Biol.
380
361-372
2008
Escherichia coli (P18956), Escherichia coli
Zhang, F.; Zheng, Q.Z.; Jiao, Q.C.; Liu, J.Z.; Zhao, G.H.
Synthesis of theanine from glutamic acid gamma-methyl ester and ethylamine catalyzed by Escherichia coli having gamma-glutamyltranspeptidase activity
Biotechnol. Lett.
32
1147-1150
2010
Escherichia coli
Kamiyama, A.; Nakajima, M.; Han, L.; Wada, K.; Mizutani, M.; Tabuchi, Y.; Kojima-Yuasa, A.; Matsui-Yuasa, I.; Suzuki, H.; Fukuyama, K.; Watanabe, B.; Hiratake, J.
Phosphonate-based irreversible inhibitors of human gamma-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity
Bioorg. Med. Chem.
24
5340-5352
2016
Escherichia coli (P18956), Escherichia coli, Homo sapiens (P19440), Homo sapiens
Lisheng, X.; Guizhen, G.; Xingtao, Z.; Mengting, W.
Enzymatic synthesis of gamma-glutamylmethylamide from L-glutamylhydrazine and methylamine catalysed by immobilized recombinant gamma-glutamyltranspeptidase
Biocatal. Biotransform.
37
86-91
2019
Escherichia coli (P18956)
-
EXTERNAL LINKS (specific for EC-Number 2.3.2.2)
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