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Information on EC 3.4.17.21 - Glutamate carboxypeptidase II and Organism(s) Rattus norvegicus and UniProt Accession P70627
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3.4.17.21 Glutamate carboxypeptidase IISpecify your search results
Word Map
- 3.4.17.21
-
tomography
-
positron
- metastases
-
psma-targeted
- node
-
lncap
-
tracer
-
prostatectomy
-
castration-resistant
-
modal
-
radioligands
- androgen
-
psma-positive
-
radiotherapy
-
radionuclide
-
68ga-psma
-
biodistribution
-
radiotracers
-
neovasculature
-
radiopharmaceutical
-
mcrpc
-
theranostic
-
pelvic
-
gleason
-
psma-expressing
-
suvmax
-
restaging
-
oligometastatic
-
68ga-labeled
-
multiparametric
-
urea-based
-
spect
-
dosimetry
-
scintigraphy
- abiraterone
-
castrate-resistant
- n-acetylaspartate
-
extraprostatic
-
mpmri
-
pet-ct
-
enzalutamide
-
18f-labeled
-
positron-emission
-
tomography-computed
-
radium-223
- pharmacology
-
radioimmunotherapy
- medicine
-
tumor-to-background
- analysis
-
radiometals
-
postprostatectomy
-
per-patient
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates
Synonyms
prostate-specific membrane antigen, gcpii, prostate specific membrane antigen, glutamate carboxypeptidase ii, naaladase, gcp ii, folh1, folate hydrolase, naag peptidase, n-acetylated alpha-linked acidic dipeptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
100 kDa ileum brush border membrane protein
-
-
-
-
Acetylaspartylglutamate dipeptidase
-
-
-
-
Dipeptidase, acetylaspartylglutamate
-
-
-
-
FGCP
-
-
-
-
Folylpoly-gamma-glutamate carboxypeptidase
-
-
-
-
I100
-
-
-
-
Ileal dipeptidylpeptidase
-
-
-
-
Membrane glutamate carboxypeptidase
-
-
-
-
mGCP
-
-
-
-
N-Acetylated alpha-linked acidic dipeptidase
N-Acetylated-alpha-linked acidic dipeptidase
-
-
-
-
N-Acetylated-alpha-linked-acidic dipeptidase
N-Acetylated-alpha-linked-amino dipeptidase
-
-
-
-
NAALA dipeptidase
-
-
-
-
NAALADase
Prostate-specific membrane antigen
-
-
-
-
Prostate-specific membrane antigen homolog
-
-
-
-
Prostrate-specific membrane antigen
-
-
-
-
PSM
-
-
-
-
PSM antigen
-
-
-
-
PSMA
-
-
-
-
Pteroylpoly-gamma-glutamate carboxypeptidase
-
-
-
-
Rat NAAG peptidase
-
-
-
-
N-Acetylated alpha-linked acidic dipeptidase
-
-
-
-
N-Acetylated-alpha-linked-acidic dipeptidase
-
-
-
-
NAALADase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
PATHWAY SOURCE
PATHWAYS
CAS REGISTRY NUMBER
COMMENTARY
111070-04-3
-
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
N-acetyl-L-aspartyl-L-glutamate + H2O
L-glutamate + N-acetyl-L-aspartate
-
-
-
-
?
N-acetyl-L-aspartyl-L-glutamate + H2O
N-acetyl-L-aspartate + L-glutamate
-
-
-
-
?
additional information
?
-
-
enzyme inhibition depresses mossy fiber-CA3 synaptic transmission
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
-
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
enantiospecific reaction
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
enzyme inhibition reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion traumatic brain injury
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
i.e. NAAG, a neurodipeptide, the enzyme acts as membrane-bound receptor being recycled through clathrin coated pits, expression regulation within cells in prostate cancer and metastasis, overview
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
i.e. NAAG, a presynaptically active endogenous neuropeptide which is cleaved by the enzyme in the extracellular space
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
supply of the primary excitatory neurotransmitter glutamate
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
the enzyme is involved in glutamate-mediated neurodegenerative disorders, enzyme inhibition is a mechanism for reduction of excitotoxic glutamate
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
i.e. NAAG
-
-
?
N-acetyl-Asp-Glu + H2O
N-acetyl-Asp + Glu
-
the enzyme converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin
-
-
?
N-Acetyl-L-Asp-L-Glu + H2O
?
-
may play a role in signaling between non-myelinating Schwann cells and peripheral axons
-
-
?
N-Acetyl-L-Asp-L-Glu + H2O
N-Acetyl-L-Asp + L-Glu
-
-
no formation of acetate
?
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
N-acetyl-L-aspartyl-L-glutamate + H2O
L-glutamate + N-acetyl-L-aspartate
-
-
-
-
?
N-acetyl-L-aspartyl-L-glutamate + H2O
N-acetyl-L-aspartate + L-glutamate
-
-
-
-
?
additional information
?
-
-
enzyme inhibition depresses mossy fiber-CA3 synaptic transmission
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
-
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
enzyme inhibition reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion traumatic brain injury
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
i.e. NAAG, a neurodipeptide, the enzyme acts as membrane-bound receptor being recycled through clathrin coated pits, expression regulation within cells in prostate cancer and metastasis, overview
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
i.e. NAAG, a presynaptically active endogenous neuropeptide which is cleaved by the enzyme in the extracellular space
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
supply of the primary excitatory neurotransmitter glutamate
-
-
?
N-acetyl-alpha-L-aspartyl-L-glutamate + H2O
N-acetyl-alpha-L-aspartate + L-glutamate
-
the enzyme is involved in glutamate-mediated neurodegenerative disorders, enzyme inhibition is a mechanism for reduction of excitotoxic glutamate
-
-
?
N-acetyl-Asp-Glu + H2O
N-acetyl-Asp + Glu
-
the enzyme converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin
-
-
?
N-Acetyl-L-Asp-L-Glu + H2O
?
-
may play a role in signaling between non-myelinating Schwann cells and peripheral axons
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-2-(3-mercaptopropyl)-pentanedioic acid
-
antinociceptide effects in the chronic constriction injury model, cell culture model of cerebral ischemia
(R)-2-(hydroxypentafluorophenylmethyl-phosphinoylmethyl)pentanedioic acid
-
neuroprotective effects in the middle cerebral artery occlusion model, cell culture model of cerebral ischemia
(S)-2-(3-mercaptopropyl)-pentanedioic acid
-
antinociceptide effects in the chronic constriction injury model, cell culture model of cerebral ischemia
(S)-2-(hydroxypentafluorophenylmethyl-phosphinoylmethyl)pentanedioic acid
-
neuroprotective effects in the middle cerebral artery occlusion model, cell culture model of cerebral ischemia
(S)-2-[3-((S)-1-carboxy-2-(4-hydroxyphenyl)ethyl)ureido]pentanedioic acid
-
i.e. inhibitor ZJ17
(S)-2-[3-((S)-1-carboxy-3-(1H-tetrazol-5-yl)propyl)ureido]pentanedioic acid
-
i.e. inhibitor ZJ38
(S)-2-[3-((S)-1-carboxy-3-(methylsulfanyl)propyl)ureido]pentanedioic acid
-
i.e. inhibitor ZJ11
(S)-2-[3-((S)-1-carboxy-3-methylbutyl)ureido]pentanedioic acid
-
i.e. inhibitor ZJ43
2-(3-sulfanylpropyl)pentanedioic acid
-
i.e. GPI-5693, attenuates cocaine-induced conditioned place preference
2-([hydroxy[3-(trifluoromethyl)benzyl]phosphoryl]methyl)pentanedioic acid
-
IC50: 55 nM
2-([hydroxy[hydroxy(phenyl)methyl]phosphoryl]methyl)pentanedioic acid
-
IC50: 55 nM
2-([hydroxy[hydroxy(pyridin-4-yl)methyl]phosphoryl]methyl)pentanedioic acid
-
IC50: 10 nM
2-[(hydroxy[[(4-methoxyphenyl)amino]methyl]phosphoryl)methyl]pentanedioic acid
-
IC50: 3 nM
2-[[(2,4-dicarboxybutyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 0.5 nM
2-[[(2-carboxy-3-phenylpropyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 2 nM
2-[[(2-carboxy-4-phenylbutyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 2 nM
2-[[(2-carboxyethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 1 nM
2-[[(2-carboxypropyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 1.5 nM
2-[[(2-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 156 nM
2-[[(3,5-difluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 49 nM
2-[[(3-aminobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 143 nM
2-[[(3-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 70 nM
2-[[(4-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 64 nM
2-[[(anilinomethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 4 nM
2-[[hydroxy(3-phenylpropyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 230 nM
2-[[hydroxy(4-methoxybenzyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 90 nM
2-[[hydroxy(4-methylbenzyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 68 nM
2-[[hydroxy(pentafluorobenzyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 82 nM. Significantly prevents neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In the chronic constrictive model of neuropathic pain, the inhibitor sifnificantly attenuats the hypersensitivity observed with saline-treated animals
2-[[[(3-fluorophenyl)(hydroxy)methyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 16 nM
2-[[[(benzylamino)methyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 59 nM
2-[[[3,5-bis(trifluoromethyl)benzyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 55 nM
2-[[[3-(benzyloxy)-2-methyl-3-oxopropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
IC50: 95 nM
2-{[2-Carboxy-3-(4-methoxy-phenylamino)-propyl]-hydroxy-phosphinoylmethyl}-pentanedioic acid
-
IC50: 3 nM
3-(2-oxotetrahydro-thiopyran-3-yl)propionic acid
-
prodrug of inhibitor 2-(3-mercaptopropyl)pentanedioic acid
3-(3-mercaptopropyl)pentanedioic acid
-
presynaptic action of enzyme inhibition, enzyme inhibition depresses mossy fiber-CA3 synaptic transmission
5-oxononane-1,3,7,9-tetracarboxylic acid
-
inhibitor possesses mGluR3 agonist activity
GPI5232
-
i.e. 2-([((hydroxypentyfluorophenyl)methyl)phosphinoyl]methyl)pentanedioic acid
N-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]-L-glutamic acid
-
i.e. inhibitor ZJ17, antinociceptive effect of the inhibitor in the rat formalin test and the rat neuropathic pain model, agonist and antagonist activity on recombinantly expressed metabotropic glutamate receptor, overview
N-[[(1S)-1-carboxy-3-(methylsulfanyl)propyl]carbamoyl]-L-glutamic acid
-
i.e. inhibitor ZJ11, antinociceptive effect of the inhibitor in the rat formalin test and the rat neuropathic pain model, agonist and antagonist activity on recombinantly expressed metabotropic glutamate receptor, overview
N-[[(1S)-1-carboxy-3-methylbutyl]carbamoyl]-L-glutamic acid
-
i.e. inhibitor ZJ43, antinociceptive effect of the inhibitor in the rat formalin test and the rat neuropathic pain model, agonist and antagonist activity on recombinantly expressed metabotropic glutamate receptor, overview
ZJ-43
-
i.e. (S)-2-[3-((S)-1-carboxy-3-methylbutyl)ureido]pentanedioic acid, the inhibitor enhances extracellular NAAG levels and reduces extracellular levels of amino acids neurotransmitter following traumatic brain injury in vivo
2-(3-mercaptopropyl)-pentanedioic acid
-
2-MPPA, specific, potent, competitive inhibition, acts neuroprotective in vivo, e.g. in case of ischemic stroke, and provides analgesia
2-(3-mercaptopropyl)pentanedioic acid
-
IC50: 90 nM. Orally bioavailable in rats
2-(3-mercaptopropyl)pentanedioic acid
-
in rat liver microsomes, 2-(3-mercaptopropyl)pentanedioic acid is gradually produced from 3-(2-oxotetrahydro-thiopyran-3-yl)propionic acid, a thiolactone derived from the compound. 2-(3-Mercaptopropyl)pentanedioic acid is detected in plasma at concentrations well above its IC50 value for GCPII following oral administration of 3-(2-oxotetrahydro-thiopyran-3-yl)propionic acid in rats
2-(phosphonomethyl)-pentanedioic acid
-
2-PMPA, specific, potent, competitive inhibition, acts neuroprotective in vivo, e.g. in case of ischemic stroke, and provides analgesia
2-(phosphonomethyl)-pentanedioic acid
-
i.e. 2-PMPA, enzyme inhibition protects the rats in vivo against ischemic injury to the brain and spinal cord, and hypoxic and metabolic injury to neuronal cells in culture
2-(phosphonomethyl)pentanedioic acid
-
i.e. 2-PMPA, a N-acetylated-alpha-linkedacidic dipeptidase inhibitor, attenuates cocaine self-administration and cocaine-induced reinstatement of drug seeking of rats
2-(phosphonomethyl)pentanedioic acid
-
i.e. 2-PMPA, inhibits cocaine-induced behavioural sensitization
2-[[hydroxy(2-phenylethyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 150 nM
2-[[hydroxy(2-phenylethyl)phosphoryl]methyl]pentanedioic acid
-
IC50: 149 nM
additional information
-
not inhibitory are pepstatin, iodoacetamide, amastatin
-
additional information
-
GCPII inhibitors are attractive candidates for clinical treatment trials in amylotrophic lateral sclerosis
-
additional information
-
design of urea-based NAAG peptidase-specific inhibitors, inhibition strategies, overview, construction of a stroke rat model and traumatic brain injury, TBI, to test inhibitor effects, overview
-
additional information
-
N-[N-((S)-1,3-dicarboxypropyl)carbamoyl]-S-3-iodo-L-tyrosine, i.e. DCIT, is a potent antagonist of the enzyme activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00009
2-(3-mercaptopropyl)pentanedioic acid
Rattus norvegicus
-
IC50: 90 nM. Orally bioavailable in rats
0.000175
2-(phosphonomethyl)-4-(5H-tetrazol-5-yl)butanoic acid
Rattus norvegicus
-
IC50: 175 nM
0.000055
2-([hydroxy[3-(trifluoromethyl)benzyl]phosphoryl]methyl)pentanedioic acid
Rattus norvegicus
-
IC50: 55 nM
0.000055
2-([hydroxy[hydroxy(phenyl)methyl]phosphoryl]methyl)pentanedioic acid
Rattus norvegicus
-
IC50: 55 nM
0.00001
2-([hydroxy[hydroxy(pyridin-4-yl)methyl]phosphoryl]methyl)pentanedioic acid
Rattus norvegicus
-
IC50: 10 nM
0.000003
2-[(hydroxy[[(4-methoxyphenyl)amino]methyl]phosphoryl)methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 3 nM
0.0000005
2-[[(2,4-dicarboxybutyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 0.5 nM
0.000002
2-[[(2-carboxy-3-phenylpropyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 2 nM
0.000002
2-[[(2-carboxy-4-phenylbutyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 2 nM
0.000001
2-[[(2-carboxyethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 1 nM
0.0000015
2-[[(2-carboxypropyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 1.5 nM
0.000156
2-[[(2-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 156 nM
0.000049
2-[[(3,5-difluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 49 nM
0.000143
2-[[(3-aminobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 143 nM
0.00007
2-[[(3-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 70 nM
0.000064
2-[[(4-fluorobenzyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 64 nM
0.000004
2-[[(anilinomethyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 4 nM
0.000059
2-[[hydroxy(3-nitrobenzyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50 59 nM
0.00023
2-[[hydroxy(3-phenylpropyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 230 nM
0.00009
2-[[hydroxy(4-methoxybenzyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 90 nM
0.000068
2-[[hydroxy(4-methylbenzyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 68 nM
0.000082
2-[[hydroxy(pentafluorobenzyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 82 nM. Significantly prevents neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In the chronic constrictive model of neuropathic pain, the inhibitor sifnificantly attenuats the hypersensitivity observed with saline-
0.00293
2-[[hydroxy(phenyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 2930 nM
0.000016
2-[[[(3-fluorophenyl)(hydroxy)methyl](hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 16 nM
0.000059
2-[[[(benzylamino)methyl](hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 59 nM
0.000055
2-[[[3,5-bis(trifluoromethyl)benzyl](hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 55 nM
0.000095
2-[[[3-(benzyloxy)-2-methyl-3-oxopropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 95 nM
0.000003
2-{[2-Carboxy-3-(4-methoxy-phenylamino)-propyl]-hydroxy-phosphinoylmethyl}-pentanedioic acid
Rattus norvegicus
-
IC50: 3 nM
0.002
3-(2-oxotetrahydro-thiopyran-3-yl)propionic acid
Rattus norvegicus
-
pH not specified in the publication, temperature not specified in the publication
0.000508
4-(3-hydroxyphenyl)-2-(phosphonomethyl)butanoic acid
Rattus norvegicus
-
IC50: 508 nM
0.000053
2-[[benzyl(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 53 nM
0.00007
2-[[benzyl(hydroxy)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 70 nM
0.000149
2-[[hydroxy(2-phenylethyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 149 nM
0.00015
2-[[hydroxy(2-phenylethyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 150 nM
0.00036
2-[[hydroxy(propyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 360 nM
0.00056
2-[[hydroxy(propyl)phosphoryl]methyl]pentanedioic acid
Rattus norvegicus
-
IC50: 560 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
withdrawal of 3,4-methylenedioxypyrovalerone reduces expression of glutamate carboxypeptidase II in the prefrontal cortex
-
-
-
amygdala, caudate-putamen, central gray, dorsal raphe, globus pallidus, hippocampus, hypothalamus, locus coerulus, medial and lateral geniculate, olfactory bulb, periaqueductal gray, solitary nucleus, spinal trigeminal nucleus, substantia nigra, superior colliculus, thalamus, corpus callosum, fornix, habenular commissure, solitary tract, stria medularis, stria therminalis
-
especially midbrain and cerebellum, quantitative detection of GCPII content in the brain by labeling with [125I]-N-[N-((S)-1,3-dicarboxypropyl)carbamoyl]-S-3-iodo-L-tyrosine is a potent antagonist of the enzyme activity
-
kidney cortex, specifically in the brush border of proximal convoluted tubules
-
expressed during late embryonal and early postnatal development. During the first prenatal week the enzyme is downregulated in myelinating Schwann cells while the total enzyme concentrations in the nerves are transiently increased
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
present in neurophil cytoplasm, absent from neuronal cytoplasm
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
involvement of the endogenous NAAG-NAALADase signaling pathway in cocaine addiction. Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats via a NAAG-mGluR2/3-mediated mechanism, overview
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). FOLH1_RAT
752
1
84540
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
84490
-
sequence of cDNA, nonglycosylated enzyme form, the extracellular domain contains nine potential N- glycosylation sites
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the enzyme is a type II membrane glycoprotein with an intracellular segment, a transmembrane domain, and an extensive extracellular domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
the extracellular domain contains nine potential glycosylation sites
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
withdrawal of 3,4-methylenedioxypyrovalerone reduces expression of glutamate carboxypeptidase II in the prefrontal cortex
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
the enzyme is a reliable in vivo marker of re-endothelialisation after percutaneous vascular intervention and that glutamate carboxypeptidase II-positron emission tomography is the first non-invasive in vivo molecular imaging technique that can demonstrate and quantify re-endothelialisation. As a further perspective, well-powered studies in patients undergoing percutaneous vascular intervention need to confirm the potential of GCPII-PET for imaging the crucial process of arterial re-endothelialisation after injuring the vessel wall
medicine
medicine
-
design of inhibitors may lead to effective neuroprotective agents, possibility to employ GCPII inhibitors in stroke therapy
medicine
-
GCPII inhibitors are attractive candidates for clinical treatment trials in amylotrophic lateral sclerosis
medicine
-
inhibitors of NAADLADase protect against chronic glutamate-mediated motor neuron degeneration and may prove therapeutic towards amyotrophic lateral sclerosis
medicine
-
NAALADase inhibition may provide a new aproach for the treatment of both neurodegenerative disorders and peripheral neuropathies
medicine
-
for establishing new strategies to treat peripheral neuropathies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Luthi-Carter, R.; Berger, U.V.; Barczak, A.K.; Enna, M.; Coyle, J.T.
Isolation and expression of rat brain cDNA encoding glutamate carboxypeptidase II
Proc. Natl. Acad. Sci. USA
95
3215-3220
1998
Rattus norvegicus (P70627)
Bzdega, T.; Turi, T.; Wroblewska, B.; She, D.; Chung, H.S.; Kim, H.; Neale, J.H.
Molecular cloning of a peptidase against N-aspartylglutamate from a rat hippocampal cDNA library
J. Neurochem.
69
2270-2277
1997
Rattus norvegicus
Robinson, M.B.; Blakely, R.D.; Couto, R.; Coyle, J.T.
Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate
J. Biol. Chem.
262
14498-14506
1987
Rattus norvegicus
Jackson, P.F.; Cole, D.C.; Slusher, B.S.; Stetz, S.L.; Ross, L.E.; Donzanti, B.A.; Trainor, D.A.
Design, synthesis and biological activity of a potent inhibitor of the neuropeptidase N-acetylated alpha-linked acidic dipeptidase
J. Med. Chem.
39
619-622
1996
Rattus norvegicus
Berger, U.V.; Schwab, M.E.
N-Acetylated alpha-linked acidic dipeptidase may be involved in axon-Schwann cell signalling
J. Neurocytol.
25
499-512
1996
Rattus norvegicus
Berger, U.V.; Carter, R.E.; McKee, M.; Coyle, J.T.
N-Acetylated alpha-linked acidic dipeptidase is expressed by non-myelinating-Schwann cells in the peripheral nervous system
J. Neurocytol.
24
9-109
1995
Rattus norvegicus
-
Serval, V.; Galli, T.; Glowinski, J.; Lavielle, S.
In vitro and in vivo inhibition of N-acetyl-L-aspartyl-L-glutamate catabolism by N-acetylated L-glutamate analogs
J. Pharmacol. Exp. Ther.
260
1093-1100
1992
Rattus norvegicus
Subasinghe, N.; Schulte, M.; Chan, M.Y.M.; Roon, R.J.; Koerner, J.F.; Johnson, R.L.
Synthesis of acyclic and dehydroaspartic acid analogues of Ac-Asp-Glu-OH and their inhibition of rat brain N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase)
J. Med. Chem.
33
2734-2744
1990
Rattus norvegicus
Serval, V.; Barbeito, L.; Pittaluga, A.; Cheramy, A.; Lavielle, S.; Glowinski, J.
Competitive inhibition of N-acetylated-alpha-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-beta-linked L-glutamate
J. Neurochem.
55
39-46
1990
Rattus norvegicus
Stauch Slusher, B.; Robinson, M.B.; Tsai, G.; Simmons, M.L.; Richards, S.S.; Coyle, J.T.
Rat brain N-acetylated alpha-linked acidic dipeptidase activity
J. Biol. Chem.
265
21297-21301
1990
Rattus norvegicus
Fuhrman, S.; Palkovits, M.; Cassidy, M.; Neale, J.H.
The regional distribution of N-acetylaspartylglutamate (NAAG) and peptidase activity against NAAG in the rat nervous system
J. Neurochem.
62
275-281
1994
Rattus norvegicus
Blakely, R.D.; Robinson, M.B.; Thompson, R.C.; Coyle, J.T.
Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate: subcellular and regional distribution, ontogeny, and the effect of lesions on N-acetylated-alpha-linked acidic dipeptidase activity
J. Neurochem.
50
1200-1209
1988
Rattus norvegicus
Slusher, B.S.; Tsai, G.; Yoo, G.; Coyle, J.T.
Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase)
J. Comp. Neurol.
315
217-229
1992
Rattus norvegicus
Jackson, P.F.; Slusher, B.S.
Design of NAALADase inhibitors: a novel neuroprotective strategy
Curr. Med. Chem.
8
949-957
2001
Rattus norvegicus
Ajit, G.T.; Corse, A.M.; Coccia, C.F.; Bilak, M.M.; Rothstein, J.D.; Slusher, B.S.
NAALADase inhibition protects motor neurons against chronic glutamate toxicity
Eur. J. Pharmacol.
471
177-184
2003
Rattus norvegicus
Nan, F.; Bzdega, T.; Pshenichkin, S.; Wroblewski, J.T.; Wroblewska, B.; Neale, J.H.; Kozikowski, A.P.
Dual function glutamate-related ligands: discovery of a novel, potent inhibitor of glutamate carboxypeptidase II possessing mGluR3 agonist activity
J. Med. Chem.
43
772-774
2000
Rattus norvegicus
Kozikowski, A.P.; Nan, F.; Conti, P.; Zhang, J.; Ramadan, E.; Bzdega, T.; Wroblewska, B.; Neale, J.H.; Pshenichkin, S.; Wroblewski, J.T.
Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase)
J. Med. Chem.
44
298-301
2001
Rattus norvegicus
Jackson, P.F.; Tays, K.L.; Maclin, K.M.; Ko, Y.S.; Li, W.; Vitharana, D.; Tsukamoto, T.; Stoermer, D.; Lu, X.C.; Wozniak, K.; Slusher, B.S.
Design and pharmacological activity of phosphinic acid based NAALADase inhibitors
J. Med. Chem.
44
4170-4175
2001
Rattus norvegicus
Majer, P.; Jackson, P.F.; Delahanty, G.; Grella, B.S.; Ko, Y.S.; Li, W.; Liu, Q.; Maclin, K.M.; Polakova, J.; Shaffer, K.A.; Stoermer, D.; Vitharana, D.; Wang, E.Y.; Zakrzewski, A.; Rojas, C.; Slusher, B.S.; Wozniak, K.M.; Burak, E.; Limsakun, T.; Tsukamoto, T.
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor
J. Med. Chem.
46
1989-1996
2003
Rattus norvegicus
Thomas, A.G.; Vornov, J.J.; Olkowski, J.L.; Merion, A.T.; Slusher, B.S.
N-Acetylated alpha-linked acidic dipeptidase converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin
J. Pharmacol. Exp. Ther.
295
16-22
2000
Rattus norvegicus
Ghadge, G.D.; Slusher, B.S.; Bodner, A.; Canto, M.D.; Wozniak, K.; Thomas, A.G.; Rojas, C.; Tsukamoto, T.; Majer, P.; Miller, R.J.; Monti, A.L.; Roos, R.P.
Glutamate carboxypeptidase II inhibition protects motor neurons from death in familial amyotrophic lateral sclerosis models
Proc. Natl. Acad. Sci. USA
100
9554-9559
2003
Rattus norvegicus
Thomas, A.G.; Wozniak, K.M.; Tsukamoto, T.; Calvin, D.; Wu, Y.; Rojas, C.; Vornov, J.; Slusher, B.S.
Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic strategy
Adv. Exp. Med. Biol.
576
327-37
2006
Homo sapiens, Rattus norvegicus
Yamamoto, T.; Hirasawa, S.; Wroblewska, B.; Grajkowska, E.; Zhou, J.; Kozikowski, A.; Wroblewski, J.; Neale, J.H.
Antinociceptive effects of N-acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the rat formalin test and in the rat neuropathic pain model
Eur. J. Neurosci.
20
483-494
2004
Homo sapiens, Rattus norvegicus
Long, J.B.; Yourick, D.L.; Slusher, B.S.; Robinson, M.B.; Meyerhoff, J.L.
Inhibition of glutamate carboxypeptidase II (NAALADase) protects against dynorphin A-induced ischemic spinal cord injury in rats
Eur. J. Pharmacol.
508
115-122
2005
Rattus norvegicus
Ghosh, A.; Heston, W.D.
Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
J. Cell. Biochem.
91
528-539
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Tsukamoto, T.; Majer, P.; Vitharana, D.; Ni, C.; Hin, B.; Lu, X.C.; Thomas, A.G.; Wozniak, K.M.; Calvin, D.C.; Wu, Y.; Slusher, B.S.; Scarpetti, D.; Bonneville, G.W.
Enantiospecificity of glutamate carboxypeptidase II inhibition
J. Med. Chem.
48
2319-2324
2005
Homo sapiens, Rattus norvegicus
Sanabria, E.R.; Wozniak, K.M.; Slusher, B.S.; Keller, A.
GCP II (NAALADase) inhibition suppresses mossy fiber-CA3 synaptic neurotransmission by a presynaptic mechanism
J. Neurophysiol.
91
182-193
2004
Rattus norvegicus
Zhong, C.; Zhao, X.; Sarva, J.; Kozikowski, A.; Neale, J.H.; Lyeth, B.G.
NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats
J. Neurotrauma
22
266-276
2005
Rattus norvegicus
Zhou, J.; Neale, J.H.; Pomper, M.G.; Kozikowski, A.P.
NAAG peptidase inhibitors and their potential for diagnosis and therapy
Nat. Rev. Drug Discov.
4
1015-1026
2005
Homo sapiens, Rattus norvegicus
Guilarte, T.R.; McGlothan, J.L.; Foss, C.A.; Zhou, J.; Heston, W.D.; Kozikowski, A.P.; Pomper, M.G.
Glutamate carboxypeptidase II levels in rodent brain using [125I]DCIT quantitative autoradiography
Neurosci. Lett.
387
141-144
2005
Mus musculus, Rattus norvegicus
Carozzi, V.A.; Canta, A.; Oggioni, N.; Ceresa, C.; Marmiroli, P.; Konvalinka, J.; Zoia, C.; Bossi, M.; Ferrarese, C.; Tredici, G.; Cavaletti, G.
Expression and distribution of high affinity glutamate transporters GLT1, GLAST, EAAC1 and of GCPII in the rat peripheral nervous system
J. Anat.
213
539-546
2008
Rattus norvegicus
Peng, X.Q.; Li, J.; Gardner, E.L.; Ashby, C.R.; Thomas, A.; Wozniak, K.; Slusher, B.S.; Xi, Z.X.
Oral administration of the NAALADase inhibitor GPI-5693 attenuates cocaine-induced reinstatement of drug-seeking behavior in rats
Eur. J. Pharmacol.
627
156-161
2010
Rattus norvegicus
Xi, Z.X.; Li, X.; Peng, X.Q.; Li, J.; Chun, L.; Gardner, E.L.; Thomas, A.G.; Slusher, B.S.; Ashby, C.R.
Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism
J. Neurochem.
112
564-576
2010
Rattus norvegicus
Ferraris, D.V.; Majer, P.; Ni, C.; Slusher, C.E.; Rais, R.; Wu, Y.; Wozniak, K.M.; Alt, J.; Rojas, C.; Slusher, B.S.; Tsukamoto, T.
delta-Thiolactones as prodrugs of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors
J. Med. Chem.
57
243-247
2014
Rattus norvegicus
Hicks, C.; Gregg, R.A.; Nayak, S.U.; Cannella, L.A.; Schena, G.J.; Tallarida, C.S.; Reitz, A.B.; Smith, G.R.; Rawls, S.M.
Glutamate carboxypeptidase II (GCPII) inhibitor 2-PMPA reduces rewarding effects of the synthetic cathinone MDPV in rats a role for N-acetylaspartylglutamate (NAAG)
Psychopharmacology
234
1671-1681
2017
Rattus norvegicus (P70627)
Endepols, H.; Mottaghy, F.M.; Simsekyilmaz, S.; Bucerius, J.; Vogt, F.; Winz, O.; Richarz, R.; Krapf, P.; Neumaier, B.; Zlatopolskiy, B.D.; Morgenroth, A.
In vivo molecular imaging of glutamate carboxypeptidase II expression in re-endothelialisation after Percutaneous balloon denudation in a rat model
Sci. Rep.
8
7411
2018
Rattus norvegicus (P70627)
EXTERNAL LINKS (specific for EC-Number 3.4.17.21)
Transporter Classification Database (TCDB): 9.B.229.1.5
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