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Information on EC 3.4.17.11 - glutamate carboxypeptidase
for references in articles please use BRENDA:EC3.4.17.11
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.17 Metallocarboxypeptidases
3.4.17.11 glutamate carboxypeptidase
IUBMB Comments
A zinc enzyme produced by pseudomonads, Flavobacterium sp. and Acinetobacter sp. Its ability to hydrolyse pteroyl-L-glutamate (folic acid) has led to its use as a folate-depleting, antitumour agent. Type example of peptidase family M20
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 3.4.17.11
- methotrexate
-
prodrugs
-
high-dose
-
antibody-directed
- leucovorin
-
hdmtx
-
methotrexate-induced
-
gene-directed
- naaladase
-
gdept
-
antibody-enzyme
- medicine
-
anti-cea
-
anti-carcinoembryonic
-
prodrug-activating
- gcpii
- 2-pmpa
-
n-acetyl-aspartyl-glutamate
-
dampa
- drug development
- diagnostics
- pharmacology
Reaction Schemes
showrelease of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups
Synonyms
glucarpidase, carboxypeptidase g2, cpdg2, glutamate carboxypeptidase, carboxypeptidase g1, carboxypeptidase g, glutamyl carboxypeptidase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
carboxypeptidase G
-
-
-
-
carboxypeptidase G1
-
-
-
-
carboxypeptidase G2
CPG2
folate hydrolase G2
-
-
-
-
glucarpidase
glutamate carboxypeptidase
glutamyl carboxypeptidase
-
-
-
-
N-pteroyl-L-glutamate hydrolase
-
-
-
-
pteroylmonoglutamic acid hydrolase G2
-
-
-
-
carboxypeptidase G2
-
-
-
-
carboxypeptidase G2
-
glutamate carboxypeptidase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
9074-87-7
not distinguishable from EC 3.4.19.9 in Chemical Abstracts
94894-32-3
Pseudomonas isoenzyme 2
94894-33-4
Pseudomonas isoenzyme 2 precursor
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzyl-L-glutamic acid + H2O
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzoic acid + L-glutamate
-
Substrates: a prodrug
Products: -
Products: -
?
(2R)-2-[([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)amino]-4-(2H-tetrazol-5-yl)butanoic acid + H2O
?
Substrates: -
Products: -
Products: -
?
(2S)-2-[([4-[bis(2-methoxyethyl)amino]-3,5-difluorophenyl]carbamoyl)amino]hexanedioic acid + H2O
?
Substrates: -
Products: -
Products: -
?
(2S)-2-[[(4-[1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]-3,3,5-trioxo-2,6-dioxa-3,6-thia-4-azaheptan-7-yl]phenoxy)carbonyl]amino]pentanedioic acid + H2O
5'-O-[([[4-(carboxyoxy)phenyl]methoxy]carbonyl)sulfamoyl]adenosine + L-glutamate
-
Substrates: AMS-5'-PHOBA-Glu, the substrate is cleaved efficiently by the enzyme, activating its cytotoxic activity
Products: -
Products: -
?
(2S)-2-[[(9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoyloxy)methyl]oxolan-2-yl]-9H-purin-6-yl)carbamoyl]amino]pentanedioic acid + H2O
?
-
Substrates: AMS-6-Glu
Products: -
Products: -
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diylcarbamoylimino])dipentanedioic acid + 2 H2O
(11aS,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one) + ?
-
Substrates: -
Products: -
Products: -
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diyloxycarbonylimino])dipentanedioic acid + 2 H2O
3-hydroxybenzyl 4-hydroxybenzyl (11S,11aS,11'S,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) + 2 N-carboxy-L-glutamate
-
Substrates: -
Products: -
Products: -
?
(4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
Substrates: a trifluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
Substrates: a difluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
Substrates: a trifluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
Substrates: a difluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
Substrates: a trifluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
Substrates: a difluorinated prodrug
Products: -
Products: -
?
2,4-dihydroxypteroyl-L-glutamic acid + H2O
2,4-dihydroxypteroate + L-Glu
-
Substrates: -
Products: -
Products: -
?
2-[([4-[bis(2-iodoethyl)amino]phenoxy]carbonyl)amino]hexanedioic acid + H2O
?
Substrates: -
Products: -
Products: -
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoic acid + H2O
?
-
Substrates: cognate drug
Products: -
Products: -
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
3,5-difluorobenzoyl-L-glutamate + H2O
3,5-difluorobenzoate + L-glutamate
Substrates: -
Products: chemical exchange saturation transfer magnetic resonance study, i.e. CEST-MR to monitor the release of glutamate. CEST-MR affords the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo
Products: chemical exchange saturation transfer magnetic resonance study, i.e. CEST-MR to monitor the release of glutamate. CEST-MR affords the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo
?
3,5-difluorobenzoyl-L-glutamic acid + H2O
3,5-difluorobenzoic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
3-fluoro-4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
4-amino-N10-methylpteroylaspartic acid + H2O
4-amino-N10-methylpteroate + Asp
-
Substrates: -
Products: -
Products: -
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + glutamate
-
Substrates: -
Products: -
Products: -
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + L-glutamate
Substrates: -
Products: -
Products: -
?
4-aminopteroylaspartic acid + H2O
4-aminopteroate + Asp
-
Substrates: -
Products: -
Products: -
?
4-[(2-chloroethyl) [2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid + H2O
4-[(2-chloroethyl) [2-(mesyloxy)ethyl]amino]benzoate + L-glutamate
Substrates: -
Products: -
Products: -
?
4-[(2-chloroethyl)(2-methylsulphonyloxyethyl)amino]benzoic acid + H2O
?
-
Substrates: cognate drug
Products: -
Products: -
?
4-[(2-chloroethyl)-(2-methylsulphonyloxyethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]benzoate + L-glutamate
Substrates: -
Products: -
Products: -
?
4-[bis(2-iodoethyl)-amino]-phenyloxycarbonyl-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
4-[bis[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid + H2O
4-[bis[2-(mesyloxy)ethyl]amino]benzoate + L-glutamate
Substrates: -
Products: -
Products: -
?
5'-O-sulfamoyladenosine-L-glutamate + H2O
? + L-glutamate
Substrates: -
Products: -
Products: -
?
7-hydroxy-methotrexate + H2O
7-hydroxy-4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
alpha-L-glutamyl-L-glutamic acid + H2O
L-Glu + L-Glu
-
Substrates: -
Products: -
Products: -
?
benzoyl-L-glutamic acid + H2O
benzoate + glutamate
-
Substrates: -
Products: -
Products: -
?
di-tert-butyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenyloxycarbonyl-L-glutamic acid + H2O
?
-
Substrates: -
Products: -
Products: -
?
diallyl 4-[N-[4'-bis(2''-chloroethyl)aminophenyl]-N-methylcarbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
Substrates: -
Products: -
Products: -
?
diallyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
Substrates: -
Products: -
Products: -
?
dihydrofolic acid + H2O
dihydropteroic acid + Glu
-
Substrates: -
Products: -
Products: -
?
gamma-L-glutamyl-L-glutamic acid + H2O
L-Glu + L-Glu
-
Substrates: -
Products: -
Products: -
?
glycyl-L-glutamic acid + H2O
glycine + glutamate
-
Substrates: -
Products: -
Products: -
?
L-tyrosyl-L-glutamic acid + H2O
tyrosine + glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-deoxy-4-amino-N10-methylpteroic acid + glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
N-([4-[(3E)-4-(4-hydroxyphenyl)hex-3-en-3-yl]phenoxy]carbonyl)-L-glutamic acid + H2O
4-[(3E)-4-(4-hydroxyphenyl)hex-3-en-3-yl]phenyl hydrogen carbonate + L-glutamate
Substrates: -
Products: -
Products: -
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenoxy]carbonyl)-L-glutamic acid + H2O
(11aS)-7,8-dimethoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one + ?
-
Substrates: -
Products: -
Products: -
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenyl]carbamoyl)-L-glutamic acid + H2O
? + L-glutamate
-
Substrates: -
Products: -
Products: -
?
N-([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]phenyl hydrogen carbonate + L-glutamate
Substrates: -
Products: -
Products: -
?
N-([4-[bis(2-iodoethyl)amino]-3,5-difluorophenoxy]carbonyl)glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorophenyl hydrogen carbonate + glutamate
Substrates: -
Products: -
Products: -
?
N-([4-[bis(2-iodoethyl)amino]-3-fluorophenoxy]carbonyl)glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3-fluorophenyl hydrogen carbonate + glutamate
Substrates: -
Products: -
Products: -
?
N-([4-[bis(2-iodoethyl)amino]phenoxy]carbonyl)glutamic acid + H2O
4-[bis(2-iodoethyl)amino]phenyl hydrogen carbonate + glutamate
Substrates: -
Products: -
Products: -
?
N-benzyloxycarbonyl-L-aspartic acid + H2O
benzyl carbonate + L-Asp
-
Substrates: -
Products: -
Products: -
?
N-benzyloxycarbonyl-L-glutamic acid + H2O
benzyl carbonate + L-Glu
-
Substrates: no activity with D-glutamic acid
Products: -
Products: -
?
N-benzyloxycarbonyl-L-glutamine + H2O
benzyl carbonate + L-Gln
-
Substrates: -
Products: -
Products: -
?
N-[(2E)-3-(4-bromophenyl)-1-methyltriaz-2-ene-1-carbonyl]-L-glutamic acid + H2O
(2E)-3-(4-bromophenyl)-1-methyltriaz-2-ene-1-carboxylic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[(4-[[([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)oxy]methyl]phenoxy)carbonyl]glutamic acid + H2O
4-[[([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)oxy]methyl]phenyl hydrogen carbonate + glutamate
Substrates: -
Products: -
Products: -
?
N-[(4-[[([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)oxy]methyl]phenyl)carbamoyl]glutamic acid + H2O
(4-[[([4-[bis(2-chloroethyl)amino]phenoxy]carbonyl)oxy]methyl]phenyl)carbamic acid + glutamate
Substrates: -
Products: -
Products: -
?
N-[(4-[[([4-[bis(2-chloroethyl)amino]phenyl]carbamoyl)oxy]methyl]phenoxy)carbonyl]glutamic acid + H2O
4-[[([4-[bis(2-chloroethyl)amino]phenyl]carbamoyl)oxy]methyl]phenyl hydrogen carbonate + glutamate
Substrates: -
Products: -
Products: -
?
N-[(4-[[([4-[bis(2-chloroethyl)amino]phenyl]carbamoyl)oxy]methyl]phenyl)carbamoyl]glutamic acid + H2O
(4-[[([4-[bis(2-chloroethyl)amino]phenyl]carbamoyl)oxy]methyl]phenyl)carbamic acid + glutamate
Substrates: -
Products: -
Products: -
?
N-[4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)-2-fluorobenzoyl]-L-glutamic acid + H2O
4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)-2-fluorobenzoic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)-3-fluorobenzoyl]-L-glutamic acid + H2O
4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)-3-fluorobenzoic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)benzoyl]-L-glutamic acid + H2O
4-(bis[2-[(methanesulfonyl)oxy]ethyl]amino)benzoic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[[4-([[(11S)-11-hydroxy-7,8-dimethoxy-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carbonyl]oxy]methyl)phenoxy]carbonyl]-L-glutamic acid + H2O
[4-(carboxyoxy)phenyl]methyl (11S)-11-hydroxy-7,8-dimethoxy-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[[4-([[(11S)-11-hydroxy-7,8-dimethoxy-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carbonyl]oxy]methyl)phenyl]carbamoyl]-L-glutamic acid + H2O
[4-([[(11S)-11-hydroxy-7,8-dimethoxy-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carbonyl]oxy]methyl)phenyl]carbamic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
N-[[4-([[(2-hydroxy-3-methyl-5-[[(1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl]oxy]cyclohexyl)carbamoyl]oxy]methyl)phenoxy]carbonyl]glutamic acid + H2O
? + glutamate
Substrates: -
Products: -
Products: -
?
N-[[4-([[(2-hydroxy-3-methyl-5-[[(1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl]oxy]cyclohexyl)carbamoyl]oxy]methyl)phenyl]carbamoyl]glutamic acid + H2O
? + glutamate
Substrates: -
Products: -
Products: -
?
N-[[4-([[[4-[bis(2-iodoethyl)amino]phenyl](methyl)carbamoyl]oxy]methyl)phenyl]carbamoyl]glutamic acid + H2O
[4-([[[4-[bis(2-iodoethyl)amino]phenyl](methyl)carbamoyl]oxy]methyl)phenyl]carbamic acid + glutamate
Substrates: -
Products: -
Products: -
?
pteroyl-gamma,gamma-triglutamate + H2O
?
-
Substrates: -
Products: -
Products: -
?
[4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
[4-[bis(2-hydroxyethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
Substrates: prodrug activated by CPG2
Products: -
Products: -
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
Substrates: inactivation of the antitumor drug
Products: -
Products: -
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
Substrates: the pharmacolically active 6S-stereoisomer is degraded faster than the inactive 6R-stereoisomer
Products: -
Products: -
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
Substrates: substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
Products: -
Products: -
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
Substrates: -
Products: -
Products: -
?
4-aminopteroylglutamic acid + H2O
4-aminopteroate + Glu
-
Substrates: i.e. aminopterin
Products: -
Products: -
?
4-aminopteroylglutamic acid + H2O
4-aminopteroate + Glu
-
Substrates: i.e. aminopterin
Products: -
Products: -
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
Substrates: i.e. leucovorin
Products: -
Products: -
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
Substrates: i.e. leucovorin
Products: -
Products: -
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
Substrates: -
Products: -
Products: -
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
Substrates: i.e. leucovorin
Products: -
Products: -
?
5-methyltetrahydrofolate + H2O
5-methylpteroate + Glu
-
Substrates: weak
Products: -
Products: -
?
5-methyltetrahydrofolate + H2O
5-methylpteroate + Glu
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + H2O
5-methylpteroate + Glu
-
Substrates: -
Products: -
Products: -
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
Substrates: the water soluble substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
Products: -
Products: -
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
Substrates: -
Products: -
Products: -
?
folate + H2O
pteroate + L-glutamate
A0A062BQA4
Substrates: -
Products: -
Products: -
?
folic acid + H2O
pteroic acid + glutamic acid
-
Substrates: -
Products: -
Products: -
?
folic acid + H2O
pteroic acid + glutamic acid
-
Substrates: -
Products: -
Products: -
?
folic acid + H2O
pteroic acid + glutamic acid
Substrates: -
Products: -
Products: -
?
folic acid + H2O
pteroic acid + glutamic acid
-
Substrates: i.e. pteroyl-L-glutamic acid
Products: -
Products: -
r
folic acid + H2O
pteroic acid + glutamic acid
-
Substrates: equilibrium lies far towards hydrolysis
Products: -
Products: -
r
folic acid + H2O
pteroic acid + glutamic acid
-
Substrates: no activity with pteroyl-D-glutamic acid
Products: -
Products: -
r
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: highly reduced clearance of the drug in enzyme-defective patients leads to severe neutropenia, mucositis, nephrotoxicity, neurotoxicity, and elevation of liver enzymes in plasma
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: i.e. amethopterin
Products: -
Products: -
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
A0A062BQA4
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
Substrates: related toxicity, overview, rapid inactivation of methotrexate by CPDG2, the product DAMPA is eliminated more raoidly than methotrexate
Products: i.e. DAMPA
Products: i.e. DAMPA
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with casein, azocasein, gelatin, bovine albumin, and human albumin
Products: -
Products: -
-
additional information
?
-
-
Substrates: releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: substituents on N5 of the pteridine ring decrease the velocity of hydrolysis
Products: -
Products: -
?
additional information
?
-
-
Substrates: synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: specifically cleaves terminal glutamic acid amines
Products: -
Products: -
?
additional information
?
-
-
Substrates: rapid hydrolysis occurs in linkages of the form RCO-Glu and RCO-Gln, whereas those of the form RCO-D-Glu (D-Glu-D-Glu and Z-D-Glu) are not attacked
Products: -
Products: -
?
additional information
?
-
-
Substrates: no hydrolysis of glutamate or glutamine lacking a free carboxyl alpha-carboxyl
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: effects of carboxypeptidase G2 administration to patients with methotrexate-induce renal failure, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: half-lives of prodrugs and drugs, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: specifically cleaves terminal glutamic acid amines
Products: -
Products: -
?
additional information
?
-
-
Substrates: CPG2 cleaves folic acid to pteroic acid and activates a range of bifunctional alkylating agent and antibiotic prodrugs
Products: -
Products: -
?
additional information
?
-
-
Substrates: hydrolyzes the COOH-terminal glutamate of oligopeptides and N-benzyloxycarbonyl glutamates
Products: -
Products: -
?
additional information
?
-
-
Substrates: lesser activity against aspartate COOH-terminal peptide linkages
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diylcarbamoylimino])dipentanedioic acid + 2 H2O
(11aS,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one) + ?
-
Substrates: -
Products: -
Products: -
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diyloxycarbonylimino])dipentanedioic acid + 2 H2O
3-hydroxybenzyl 4-hydroxybenzyl (11S,11aS,11'S,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) + 2 N-carboxy-L-glutamate
-
Substrates: -
Products: -
Products: -
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
Substrates: a difluorinated prodrug
Products: -
Products: -
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
Substrates: a difluorinated prodrug
Products: -
Products: -
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
Substrates: inactivation of the antitumor drug
Products: -
Products: -
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
Substrates: substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
Products: -
Products: -
?
7-hydroxy-methotrexate + H2O
7-hydroxy-4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: -
Products: -
Products: -
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
Substrates: the water soluble substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
Products: -
Products: -
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
Substrates: highly reduced clearance of the drug in enzyme-defective patients leads to severe neutropenia, mucositis, nephrotoxicity, neurotoxicity, and elevation of liver enzymes in plasma
Products: -
Products: -
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
Substrates: related toxicity, overview, rapid inactivation of methotrexate by CPDG2, the product DAMPA is eliminated more raoidly than methotrexate
Products: i.e. DAMPA
Products: i.e. DAMPA
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenoxy]carbonyl)-L-glutamic acid + H2O
(11aS)-7,8-dimethoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one + ?
-
Substrates: -
Products: -
Products: -
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenyl]carbamoyl)-L-glutamic acid + H2O
? + L-glutamate
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: specifically cleaves terminal glutamic acid amines
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: effects of carboxypeptidase G2 administration to patients with methotrexate-induce renal failure, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: specifically cleaves terminal glutamic acid amines
Products: -
Products: -
?
additional information
?
-
-
Substrates: CPG2 cleaves folic acid to pteroic acid and activates a range of bifunctional alkylating agent and antibiotic prodrugs
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
Zn2+
-
each subunit of the dimer constists of a larger catalytic domain containing two zinc ions at the active site and a separate smaller domain that forms the dimer interface
Zn2+
-
contains 4 atoms of zinc per enzyme molecule, which are required for full activity
Zn2+
-
is the only heavy metal ion capable of restoring full activity when the endogenous metal is removed by incubation with the chelating resin
additional information
Mg2+ inhibits the activity of the recombinant enzyme
additional information
-
Mg2+ inhibits the activity of the recombinant enzyme
additional information
Mn2+ inhibits the activity of the recombinant enzyme
additional information
-
Mn2+ inhibits the activity of the recombinant enzyme
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-2-[(3-aminonaphthalene-2-carbonyl)amino]pentanedioic acid
CP06
(2R)-2-[[3-(2-methylpropanamido)naphthalene-2-carbonyl]amino]pentanedioic acid
CP67
(4-[bis(2-chloroethyl)amino]-2,3,5,6-tetrafluorobenzoyl)-L-glutamic acid
-
prodrug, competitive inhibition
(4-[bis(2-iodoethyl)amino]-2,3,5,6-tetrafluorobenzoyl)-L-glutamic acid
-
prodrug, competitive inhibition
4-Aminopteroylaspartic acid
-
hydrolysis of 4-amino-N10-methylpteroylglutamic acid
ethanol
-
by raising methanol levels to 2.5 and 5% (v/v), the relative activity of the enzyme decreases to 83.8% and 34.7%, respectively
glycerol
-
the activity of the enzyme decreases by 21% and 56%, respectively, by increments of 2.5 and 5% (v/v) of glycerol
Isopropyl alcohol
-
1% (v/v) isopropyl alcohol completely halts the enzymatic activity
L-aspartic acid
-
weak inhibition of hydrolysis of 4-amino-N10-methylpteroylglutamic acid
methanol
-
by raising methanol levels to 2.5 and 5% (v/v), the relative activity of the enzyme decreases to 61.7% and 4%, respectively
N-Benzyloxycarbonyl glutamic acid
-
hydrolysis of 4-amino-N10-methylpteroylglutamic acid
N-Benzyloxycarbonylaspartic acid
-
hydrolysis of 4-amino-N10-methylpteroylglutamic acid
EDTA
-
the enzyme activity is strongly inhibited when EDTA sequesteres zinc ions (11% residual activity at 1 mM)
L-Glutamic acid
-
hydrolysis of 4-amino-N10-methylpteroylglutamic acid, no inhibition by D-glutamic acid
additional information
-
in vitro cytotoxicity of the prodrugs in LS174T colon cell line, overview
-
additional information
Mg2+ inhibits the activity of the recombinant enzyme; Mn2+ inhibits the activity of the recombinant enzyme
-
additional information
-
Mg2+ inhibits the activity of the recombinant enzyme; Mn2+ inhibits the activity of the recombinant enzyme
-
additional information
-
orally available glutamate carboxypeptidase inhibitor E2072 (commercial preparation) has a neuroprotective effect on three well-established animal models of chemotherapy. It improves the chemotherapy-induced nerve conduction velocity deficits
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acute Kidney Injury
Acute renal failure post high dose methotrexate infusion successfully managed with high dose folinic Acid and high flux dialysis.
Acute Kidney Injury
Carboxypeptidase G2 rescue in a 79 year-old patient with cranial lymphoma after high-dose methotrexate induced acute renal failure.
Acute Kidney Injury
Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.
Acute Kidney Injury
Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High-Dose Methotrexate Therapy.
Acute Kidney Injury
Fixed-Dose Glucarpidase for Toxic Methotrexate Levels and Acute Kidney Injury in Adult Lymphoma Patients: Case Series.
Acute Kidney Injury
Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy.
Acute Kidney Injury
Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.
Autoimmune Diseases
Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains.
Brain Injuries
Neuroprotective effects of a dendrimer-based glutamate carboxypeptidase inhibitor on superoxide dismutase transgenic mice after neonatal hypoxic-ischemic brain injury.
Breast Neoplasms
Combined impact of polymorphism of folate metabolism genes; glutamate carboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in kashmiri women.
Breast Neoplasms
Regressions of established breast carcinoma xenografts by carboxypeptidase G2 suicide gene therapy and the prodrug CMDA are due to a bystander effect.
Carcinoma
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Carcinoma
Suicide gene therapy of human colon carcinoma xenografts using an armed oncolytic adenovirus expressing carboxypeptidase G2.
Carcinoma, Hepatocellular
Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2.
Carcinoma, Non-Small-Cell Lung
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Choriocarcinoma
The potential of carboxypeptidase G2-antibody conjugates as anti-tumour agents. I. Preparation of antihuman chorionic gonadotrophin-carboxypeptidase G2 and cytotoxicity of the conjugate against JAR choriocarcinoma cells in vitro.
Choriocarcinoma
The potential of carboxypeptidase G2: antibody conjugates as anti-tumour agents. II. In vivo localising and clearance properties in a choriocarcinoma model.
Colonic Neoplasms
Carboxypeptidase G2 and trimetrexate cause growth delay of human colonic cancer cells in vitro.
Colorectal Neoplasms
Antibody-directed enzyme prodrug therapy: efficacy and mechanism of action in colorectal carcinoma.
Colorectal Neoplasms
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Hodgkin Disease
Successful carboxypeptidase G2 rescue of a high-risk elderly Hodgkin lymphoma patient with methotrexate intoxication and renal failure.
Leukemia
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Liver Neoplasms
Plasma glutamate carboxypeptidase is a negative regulator in liver cancer metastasis.
Lung Neoplasms
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Lung Neoplasms
Hypermethylation of PGCP gene is associated with human bronchial epithelial cells immortalization.
Lymphoma
Carboxypeptidase G2 rescue in a 79 year-old patient with cranial lymphoma after high-dose methotrexate induced acute renal failure.
Lymphoma
Fixed-Dose Glucarpidase for Toxic Methotrexate Levels and Acute Kidney Injury in Adult Lymphoma Patients: Case Series.
Lymphoma
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Medulloblastoma
Comparative effects of citrovorum factor and carboxypeptidase G1 on cerebrospinal fluid-methotrexate pharmacokinetics.
Melanoma
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Neoplasm Metastasis
Plasma glutamate carboxypeptidase is a negative regulator in liver cancer metastasis.
Neoplasms
Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds.
Neoplasms
Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey.
Neoplasms
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Neoplasms
Biodistribution of an antibody-enzyme conjugate for antibody-directed enzyme prodrug therapy in nude mice bearing a human colon adenocarcinoma xenograft.
Neoplasms
Catalytic activity of an in vivo tumor targeted anti-CEA scFv::carboxypeptidase G2 fusion protein.
Neoplasms
Characterisation of the Carboxypeptidase G2 Catalytic Site and Design of New Inhibitors for Cancer Therapy.
Neoplasms
Characterization of a Stable Form of Carboxypeptidase G2 (Glucarpidase), a Potential Biobetter Variant, From Acinetobacter sp. 263903-1.
Neoplasms
Coupling of a Novel TIMP3 Peptide to Carboxypeptidase G2 for Pro-Drug Activation at the Tumour Site.
Neoplasms
Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy.
Neoplasms
Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance.
Neoplasms
Engineering carboxypeptidase G2 circular permutations for the design of an autoinhibited enzyme.
Neoplasms
Functional overexpression and purification of a codon optimized synthetic glucarpidase (carboxypeptidase G2) in Escherichia coli.
Neoplasms
Glucarpidase (carboxypeptidase g2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy.
Neoplasms
Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity.
Neoplasms
In vitro studies on CNGRC-CPG2 fusion proteins for ligand-directed enzyme prodrug therapy for targeted cancer therapy.
Neoplasms
Inactivation and clearance of an anti-CEA carboxypeptidase G2 conjugate in blood after localisation in a xenograft model.
Neoplasms
Induction of apoptosis by the ADEPT agent ZD2767: comparison with the classical nitrogen mustard chlorambucil and a monofunctional ZD2767 analogue.
Neoplasms
Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment.
Neoplasms
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Neoplasms
Modifying an immunogenic epitope on a therapeutic protein: a step towards an improved system for antibody-directed enzyme prodrug therapy (ADEPT).
Neoplasms
Novel prodrugs of alkylating agents derived from 2-fluoro- and 3-fluorobenzoic acids for antibody-directed enzyme prodrug therapy.
Neoplasms
Novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase G2.
Neoplasms
Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).
Neoplasms
Production of "biobetter" glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment.
Neoplasms
Production of "biobetter" variants of glucarpidase with enhanced enzyme activity.
Neoplasms
Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.
Neoplasms
Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains.
Neoplasms
Suicide gene therapy of human colon carcinoma xenografts using an armed oncolytic adenovirus expressing carboxypeptidase G2.
Neoplasms
Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2.
Neoplasms
Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models.
Neoplasms
Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2.
Neural Tube Defects
Role of parental folate pathway single nucleotide polymorphisms in altering the susceptibility to neural tube defects in South India.
Osteosarcoma
2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.
Osteosarcoma
Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High-Dose Methotrexate Therapy.
Peripheral Nervous System Diseases
Glutamate Carboxypeptidase Inhibition Reduces the Severity of Chemotherapy-Induced Peripheral Neurotoxicity in Rat.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Novel risk factors for glucarpidase use in pediatric acute lymphoblastic leukemia: Hispanic ethnicity, age, and the ABCC4 gene.
Prostatic Neoplasms
68Ga/64Cu PSMA bio-distribution in prostate cancer patients: potential pitfalls for different tracers.
Prostatic Neoplasms
A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules.
Prostatic Neoplasms
Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer.
Prostatic Neoplasms
Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey.
Prostatic Neoplasms
Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients.
Prostatic Neoplasms
Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer.
Renal Insufficiency
Carboxypeptidase G2 rescue in delayed methotrexate elimination in renal failure.
Renal Insufficiency
Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure.
Renal Insufficiency
Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications.
Renal Insufficiency
Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure.
Renal Insufficiency
Successful carboxypeptidase G2 rescue in delayed MTX-elimination due to renal failure.
Renal Insufficiency
Successful carboxypeptidase G2 rescue of a high-risk elderly Hodgkin lymphoma patient with methotrexate intoxication and renal failure.
Renal Insufficiency
[Carboxypeptidase-G2-rescue in a woman with methotrexate-induced renal failure]
Stomach Neoplasms
Gene polymorphisms of folate metabolizing enzymes and the risk of gastric cancer.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0034
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzyl-L-glutamic acid
-
pH 7.3, 37 °C
0.0011
(4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0012
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0026
(4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0017
(4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0028
(4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0017
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
0.0013
di-tert-butyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenyloxycarbonyl-L-glutamic acid
-
-
0.00605
diallyl 4-[N-[4'-bis(2''-chloroethyl)aminophenyl]-N-methylcarbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid
-
-
0.00055
diallyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid
-
-
0.0065
methotrexate
-
at pH 7.5, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
583
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzyl-L-glutamic acid
-
pH 7.3, 37 °C
825
(4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
827
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
1150
(4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
732
(4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
220
(4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
1150
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid
-
pH 7.3, 37 °C
5.5
diallyl 4-[N-[4'-bis(2''-chloroethyl)aminophenyl]-N-methylcarbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid
-
-
2.9
diallyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid
-
-
4.57
methotrexate
-
at pH 7.5, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00011
(2S)-2-[[(4-[1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]-3,3,5-trioxo-2,6-dioxa-3,6-thia-4-azaheptan-7-yl]phenoxy)carbonyl]amino]pentanedioic acid
-
pH and temperature not specified in the publication
-
0.00000065
(2S)-2-[[(9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoyloxy)methyl]oxolan-2-yl]-9H-purin-6-yl)carbamoyl]amino]pentanedioic acid
-
pH and temperature not specified in the publication
700
methotrexate
-
at pH 7.5, temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.068
(2R)-2-[(3-aminonaphthalene-2-carbonyl)amino]pentanedioic acid
Pseudomonas sp. RS-16
pH 7.3, 37°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
7.3
7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.5
6 - 8.5
A0A062BQA4
more than 45% of the maximum activity is retained at pH 6.0-8.5
6 - 8.5
more than 45% of the maximum activity is retained at pH 6.0-8.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
with methotrexate and 5-methyltetrahydrofolate as substrates, the reaction proceeds equally well between 30°C and 42°C
37
50
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 60
30 - 60
A0A062BQA4
about 60% activity is retained between 30 and 60°C
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
brenda
human cancer cell lines are targeted by a vector carrying the CPG2 gene, CPG2 gene originates from different organism
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
strong expression in the epidermal layer of the scutellum of 10-DAP embryos
brenda
additional information
additional information
transcripts are detected throughout the whole plant body except the endosperm
brenda
additional information
-
transcripts are detected throughout the whole plant body except the endosperm
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PLAT3_ORYSJ
749
0
81009
Swiss-Prot
other Location (Reliability: 4)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
83000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D141A
substitution leads to a decrease in expression level (compared to wild type). Melting temperature is 53.2°C, compared to 60.4°C for wild-type enzyme
E175A
substitution leads to a decrease in expression level (compared to wild type). Melting temperature is 71.4°C, compared to 60.4°C for wild-type enzyme. Mutation abolishes activity against methotrexate
E200A
substitution leads to a decrease in expression level (compared to wild type). Melting temperature is 64.3°C, compared to 60.4°C for wild-type enzyme
G123S
the variant has increased catalytic efficiency relative to wild type enzyme. The mutant enzyme has higher alpha-helical content relative to the wild type enzyme
H112A
substitution leads to a high decrease in expression level (compared to wild type). Melting temperature is 28.2°C, compared to 60.4°C for wild-type enzyme
H385A
substitution leads to a low decrease in expression level (compared to wild type). Melting temperature is 55.1°C, compared to 60.4°C for wild-type enzyme
I100T
the variant has increased catalytic efficiency relative to wild type enzyme. The mutant enzyme has higher alpha-helical content relative to the wild type enzyme
K208A
substitution leads to a high decrease in expression level (compared to wild type). Melting temperature is 53.4°C, compared to 60.4°C for wild-type enzyme. Mutation abolishes activity against methotrexate
S210A
substitution leads to a high decrease in expression level (compared to wild type). Melting temperature is 54.4C, compared to 60.4°C for wild-type enzyme. Mutation abolishes activity against methotrexate
T239A
the variant has increased catalytic efficiency relative to wild type enzyme. The mutant enzyme has higher alpha-helical content relative to the wild type enzyme
T357A
substitution leads to a decrease in expression level (compared to wild type). Melting temperature is 55.4°C, compared to 60.4°C for wild-type enzyme. Mutation abolishes activity against methotrexate
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 10
5 - 10
A0A062BQA4
the enzyme retains more than 80% activity after 1 h incubation at pH 5.0-10.0
5 - 10
the enzyme retains more than 60% activity after 1 h incubation at pH 5.0-10.0
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 70
30 - 43
-
the half-lifes of the enzyme at 30, 37, 40, and 43°C are about 2012, 683, 248 and 181 min, respectively . The enzyme is irreversibly inactivated by increasing temperature
20 - 70
A0A062BQA4
the enzyme exhibits thermostability up to 60°C with more than 50% activity remaining after incubation at this temperature for 1 h. However, it is almost completely inactive at 70°C
20 - 70
the enzyme exhibits thermostability up to 40°C with more than 90% activity remaining after incubation for 1 h. The enzyme activity drops sharply at 50°C to less than 40% and is almost zero at 60°C
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activity can increase up to 30% if the enzyme at all stages of purification is stored at -20°C
-
the enzyme is resistant to chymotrypsin and pepsin, but it is completely digested by a proteinase K
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 0.01 M Tris-chloride buffer, pH 7.3, 0.01 mM ZnCl2, stable for several months
-
4°C, 0.01 M Tris-chloride buffer, pH 7.3, 0.01 mM ZnCl2, stable for 2 to 3 weeks
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
as His-tagged protein in a single step by Ni2+ charged column chromatography
chitin affinity columnchromatography and Q-Sepharose column chromatography
-
Ni-NTA agarose column chromatography
SP-Sephadex column chromatography and DEAE-C ion-exchange chromatography or Ni2+-charged column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
high-yield expression in Escherichia coli, expression of the full-length enzyme, as well as protein fragments corresponding to the individual catalytic and dimerization domains
into a binary vector for Agrobacterium tumefaciens-mediated transformation
overexpression of a codon-optimized gene in Escherichia coli, vector pET28a, the enzyme is expressed to about 60% of the total host protein and the purification of the recombinant His-tagged protein could be achieved in a single step by Ni2+ charged column chromatography
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
Refolding is initiated by rapid 25fold dilution of the denatured protein into refolding buffer (100 mM Tris-HCl, pH 8.5, containing 0.1 mM EDTA and 0.5 M arginine)
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
the enzyme is used in targeted cancer strategies such as antibody-directed enzyme prodrug therapy
drug development
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs
medicine
pharmacology
the enzyme is used in antibody directed enzyme prodrug therapy to catalyse the formation of an active drug from an inert prodrug. Free carboxypeptidase G2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient
medicine
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs
medicine
-
the enzyme is used in antibody-directed enzyme prodrug therapy, ADEPT, e.g. against colorectal carcinoma expressing carcinoembryonic antigen, overview
medicine
-
potential use in antibody directed enzyme prodrug therapy (ADEPT)
medicine
-
CPG2 possesses several properties that make it suitable for suicide gene therapy
medicine
-
CPG2 possesses several properties that make it suitable for suicide gene therapy
medicine
-
carboxypeptidase G2 is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). These therapeutic strategies would benefit from robust imaging strategies that afford high spatial and temporal resolution images of the biodistribution of carboxypeptidase G2 activity. Employing dynamic nuclear polarization (DNP) and natural abundance 13C magnetic resonance spectroscopy (MRS), the carboxypeptidase G2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid to 3,5-difluorobenzoic acid and L-glutamic acid is observed in vitro. The potential for translation in vivo will primarily depend on the 13C relaxation times and this appears to be an important limiting factor in the case of 3,5-difluorobenzoyl-L-glutamic acid
medicine
-
glutamate carboxypeptidase inhibition is evident for a neuroprotective role in several chronic models of chemotherapy-induced peripheral neuropathy and claims an approach for the clinical treatment of this pathology
medicine
glutamate chemical exchange saturation transfer magnetic resonance imaging GluCEST-MRI is an attractive method for metabolic imaging of glutamate. The change in glutamate concentration measured with GluCEST MRI could provide a noninvasive biomarker of carboxypeptidase G2 activity, in addition to acting as a surrogate for prodrug activation and the concentration of activated drug in the tumor
medicine
the enzyme is used in drug detoxification when cancer patients have excessive levels of the anti-cancer agent methotrexate
medicine
design of a series of circular permutations of the medically important enzyme, carboxypeptidase G2, that show similar structure and stability to the wild-type, while retaining equivalent enzymatic activity in most cases. One of the circular permutants confers methotrexate resistance when expressed in Escherichia coli similarly to wild-type carboxypeptidase G2. The circular permutants provide a promising starting point for generating a protease regulatable form of carboxypeptidase G2, which will be valuable in advancing directed enzyme-prodrug chemotherapy technology
medicine
side effects of methotrexate especially hepatotoxicity limits clinical applications of this anticancer agent. Carboxypeptidase G2 fused to the transactivator transduction domain (TAT) is administrated for the treatment of elevated plasma concentrations of methotrexate. TAT-CPG2 significantly prevents methotrexate-induced oxidative stress by decreasing the formation of reactive oxygen species (ROS) and increasing the content of glutathione (GSH) and catalase activity. Both native and denatured TAT-carboxypeptidase G2 strongly protect HepG2 cells against methotrexate-induced oxidative stress and apoptosis. Intracellular delivery of carboxypeptidase G2 might provide a new therapeutic strategy for protecting against methotrexate mediated cytotoxicity
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McCullough, J.L.; Chabner, B.A.; Bertino, J.R.
Purification and properties of carboxypeptidase G 1
J. Biol. Chem.
246
7207-7213
1971
Stutzerimonas stutzeri
brenda
Goldman, P.; Levy, C.C.
Carboxypeptidase G: purification and properties
Proc. Natl. Acad. Sci. USA
58
1299-1306
1967
Pseudomonas sp.
brenda
Albrecht, A.M.; Boldizsar, E.; Hutchinson, D.J.
Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin
J. Bacteriol.
134
506-513
1978
Flavobacterium sp.
brenda
Sherwood, R.F.; Melton, R.G.; Alwan, S.M.; Hughes, P.
Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method
Eur. J. Biochem.
148
447-453
1985
Pseudomonas sp.
brenda
Lloyd, L.F.; Collyer, C.A.; Sherwood, R.F.
Crystallization and preliminary crystallographic analysis of carboxypeptidase G2 from Pseudomonas sp. strain RS-16
J. Mol. Biol.
220
17-18
1991
Pseudomonas sp.
brenda
Rowsell, S.; Pauptit, R.A.; Tucker, A.D.; Melton, R.G.; Blow, D.M.; Brick, P.
Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy
Structure
5
337-347
1997
Pseudomonas sp.
brenda
Niculescu-Duvaz, D.; Niculescu-Duvaz, I.; Friedlos, F.; Martin, J.; Lehouritis, P.; Marais, R.; Springer, C.J.
Self-immolative nitrogen mustards prodrugs cleavable by carboxypeptidase G2 (CPG2) showing large cytotoxicity differentials in GDEPT
J. Med. Chem.
46
1690-1705
2003
Pseudomonas sp.
brenda
Masterson, L.A.; Spanswick, V.J.; Hartley, J.A.; Begent, R.H.; Howard, P.W.; Thurston, D.E.
Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy
Bioorg. Med. Chem. Lett.
16
252-256
2006
Homo sapiens
brenda
Buchen, S.; Ngampolo, D.; Melton, R.G.; Hasan, C.; Zoubek, A.; Henze, G.; Bode, U.; Fleischhack, G.
Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure
Br. J. Cancer
92
480-487
2005
Pseudomonas sp.
brenda
Hempel, G.; Lingg, R.; Boos, J.
Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications
Cancer Chemother. Pharmacol.
55
347-353
2005
Homo sapiens
brenda
Davies, L.C.; Friedlos, F.; Hedley, D.; Martin, J.; Ogilvie, L.M.; Scanlon, I.J.; Springer, C.J.
Novel fluorinated prodrugs for activation by carboxypeptidase G2 showing good in vivo antitumor activity in gene-directed enzyme prodrug therapy
J. Med. Chem.
48
5321-5328
2005
Pseudomonas sp.
brenda
Mayer, A.; Francis, R.J.; Sharma, S.K.; Tolner, B.; Springer, C.J.; Martin, J.; Boxer, G.M.; Bell, J.; Green, A.J.; Hartley, J.A.; Cruickshank, C.; Wren, J.; Chester, K.A.; Begent, R.H.
A phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody-enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug
Clin. Cancer Res.
12
6509-6516
2006
Pseudomonas aeruginosa
brenda
Pedone, E.; Searle, F.; Brocchini, S.
Diethylstilbestrol glutamate as a potential substrate for ADEPT
J. Drug Target.
14
437-443
2006
Pseudomonas sp.
brenda
Friedlos, F.; Lehouritis, P.; Ogilvie, L.; Hedley, D.; Davies, L.; Bermudes, D.; King, I.; Martin, J.; Marais, R.; Springer, C.J.
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy
Clin. Cancer Res.
14
4259-4266
2008
Pseudomonas sp.
brenda
Mancini, L.; Davies, L.; Friedlos, F.; Falck-Miniotis, M.; Dzik-Jurasz, A.S.; Springer, C.J.; Leach, M.O.; Payne, G.S.
A novel technique to monitor carboxypeptidase G2 expression in suicide gene therapy using (19)F magnetic resonance spectroscopy
NMR Biomed.
22
561-566
2009
Homo sapiens
brenda
Kawakatsu, T.; Taramino, G.; Itoh, J.I.; Allen, J.; Sato, Y.; Hong, S.K.; Yule, R.; Nagasawa, N.; Kojima, M.; Kusaba, M.; Sakakibara, H.; Sakai, H.; Nagato, Y.
PLASTOCHRON3/GOLIATH encodes a glutamate carboxypeptidase required for proper development in rice
Plant J.
58
1028-1040
2009
Oryza sativa (Q852M4), Oryza sativa
brenda
Jamin, Y.; Gabellieri, C.; Smyth, L.; Reynolds, S.; Robinson, S.P.; Springer, C.J.; Leach, M.O.; Payne, G.S.; Eykyn, T.R.
Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity
Magn. Reson. Med.
62
1300-1304
2009
Pseudomonas sp.
brenda
Carozzi, V.A.; Chiorazzi, A.; Canta, A.; Lapidus, R.G.; Slusher, B.S.; Wozniak, K.M.; Cavaletti, G.
Glutamate carboxypeptidase inhibition reduces the severity of chemotherapy-induced peripheral neurotoxicity in rat
Neurotox. Res.
17
380-391
2010
Rattus norvegicus
brenda
Goda, S.K.; Rashidi, F.A.; Fakharo, A.A.; Al-Obaidli, A.
Functional overexpression and purification of a codon optimized synthetic glucarpidase (carboxypeptidase G2) in Escherichia coli
Protein J.
28
435-442
2009
Pseudomonas sp. (P06621), Pseudomonas sp.
brenda
Jamin, Y.; Eykyn, T.R.; Poon, E.; Springer, C.J.; Robinson, S.P.
Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance
Mol. Imaging Biol.
16
152-157
2014
Pseudomonas sp. (P06621)
brenda
Al-Qahtani, A.D.; Bashraheel, S.S.; Rashidi, F.B.; OConnor, C.D.; Romero, A.R.; Domling, A.; Goda, S.K.
Production of "biobetter" variants of glucarpidase with enhanced enzyme activity
Biomed. Pharmacother.
112
108725
2019
Pseudomonas sp. RS-16 (P06621)
brenda
Jeyaharan, D.; Brackstone, C.; Schouten, J.; Davis, P.; Dixon, A.M.
Characterisation of the carboxypeptidase G2 catalytic site and design of new inhibitors for cancer therapy
ChemBioChem
19
1959-1968
2018
Pseudomonas sp. RS-16 (P06621)
brenda
Yachnin, B.J.; Khare, S.D.
Engineering carboxypeptidase G2 circular permutations for the design of an autoinhibited enzyme
Protein Eng. Des. Sel.
30
321-331
2017
Pseudomonas sp. RS-16 (P06621)
brenda
Jeyaharan, D.; Aston, P.; Garcia-Perez, A.; Schouten, J.; Davis, P.; Dixon, A.M.
Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains
Protein Expr. Purif.
127
44-52
2016
Pseudomonas sp. RS-16 (P06621)
brenda
Sadeghian, I.; Khalvati, B.; Ghasemi, Y.; Hemmati, S.
TAT-mediated intracellular delivery of carboxypeptidase G2 protects against methotrexate-induced cell death in HepG2 cells
Toxicol. Appl. Pharmacol.
346
9-18
2018
Pseudomonas sp. RS-16 (P06621)
brenda
Khodakarami, A.; Dabirmanesh, B.; Asad, S.; Khaledi, M.
Enhanced solubility and one-step purification of functional dimeric carboxypeptidase G2
Biochemistry (Moscow)
86
190-196
2021
Pseudomonas sp. RS16
brenda
Naeemi, S.M.; Aminzadeh, S.; Sari, S.; Nemati, F.; Naseroleslami, M.
In vitro and in silico characterization of a novel glutamate carboxypeptidase from Cohnella sp. A01
Biochimie
207
83-95
2023
Cohnella sp. A01
brenda
Moradbeygi, F.; Ghasemi, Y.; Farmani, A.R.; Hemmati, S.
Glucarpidase (carboxypeptidase G2) Biotechnological production, clinical application as a methotrexate antidote, and placement in targeted cancer therapy
Biomed. Pharmacother.
166
115292
2023
Pseudomonas sp. RS-16 (P06621)
brenda
Sadeghian, I.; Hemmati, S.
Characterization of a stable form of carboxypeptidase G2 (glucarpidase), a potential biobetter variant, from Acinetobacter sp. 263903-1
Mol. Biotechnol.
63
1155-1168
2021
Acinetobacter sp. 263903-1 (A0A062BQA4), Pseudomonas sp. RS-16 (P06621)
brenda
Lee, J.P.; Corless, B.C.; Gardner, T.J.; Scheinberg, D.A.; Tan, D.S.
Development of a p-hydroxybenzyl-alcohol-linked glutamate prodrug for activation by Pseudomonas carboxypeptidase G2
Org. Lett.
25
6295-6299
2023
Pseudomonas sp.
brenda
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