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Information on EC 3.4.19.9 - folate gamma-glutamyl hydrolase and Organism(s) Homo sapiens
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3.4.19.9 folate gamma-glutamyl hydrolaseIUBMB Comments
The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-gamma-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH2 from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants. In peptidase family C26.
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Word Map
- 3.4.19.9
- polyglutamates
- methotrexate
-
polyglutamylation
- antifolate
- casei
- monoglutamates
- pteroylpolyglutamate
- sumo
-
monoglutamylated
- 5-methyltetrahydrofolate
-
deconjugation
-
trienzyme
- pentaglutamate
- rad6
- diglutamate
-
punicic
- medicine
- analysis
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
(n-1)
=
+
(n-1)
Synonyms
conjugase, gamma-glutamyl hydrolase, folate conjugase, folylpolyglutamate hydrolase, gamma-gh, leggh2, leggh3, zgammagh, leggh1, low gamma-glutamyl hydrolase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
carboxypeptidase G
-
-
-
-
conjugase
FGPH
-
-
-
-
folate conjugase
-
-
-
-
folic acid conjugase
-
-
-
-
folylpolyglutamate hydrolase
-
-
-
-
gamma-Glu-X carboxypeptidase
-
-
-
-
gamma-glutamyl hydrolase
GGH
hydrolase, gamma-glutamyl
-
-
-
-
lysosomal gamma-glutamyl carboxypeptidase
-
-
-
-
poly(gamma-glutamic acid) endohydrolase
-
-
-
-
poly(glutamic acid) hydrolase II
-
-
-
-
polyglutamate hydrolase
-
-
-
-
pteroyl-poly-gamma-glutamate hydrolase
-
-
-
-
pteroylpoly-gamma-glutamyl hydrolase
-
-
-
-
conjugase
-
-
-
-
gamma-glutamyl hydrolase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
tetrahydropteroyl-(gamma-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate
tetrahydropteroyl-(gamma-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate
catalytic mechanism, the enzyme releases mono- or di-glutamate
-
tetrahydropteroyl-(gamma-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate
Tyr36 is catalytically essential
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
tetrahydropteroyl-poly-gamma-glutamyl gamma-glutamyl hydrolase
The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-gamma-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH2 from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants. In peptidase family C26.
CAS REGISTRY NUMBER
COMMENTARY
9074-87-7
not distinguishable from EC 3.4.17.11 in Chemical Abstracts
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
methotrexate hexaglutamate + H2O
methotrexate pentaglutamate + methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate
-
-
-
?
methotrexate pentaglutamate + H2O
methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate + L-glutamate
-
-
-
?
methotrexate triglutamate + H2O
methotrexate monoglutamate + methotrexate diglutamate + glutamate
-
-
-
-
?
pteroylglutamylhexaglutamate + H2O
short-chain pteroylglutamates
-
-
after 60 min incubation, pteroylglutamate is the major product after 120 min, with quantitative recovery of free glutamate, enzyme is an exopeptidase which progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
-
removal of the poly-gamma-glutamate chains
-
-
?
polyglutamylfolate + H2O
?
-
the ability of the gamma polyglutamate and the inability of the alpha polyglutamate to serve as substrate confirm the requirement for a terminal gamma peptide bond
-
-
?
polyglutamylfolate + H2O
?
-
sequential hydrolysis of glutamates with the dissociation of substrate from enzymic surface following cleavage of each glutamate seems likely
-
-
?
polyglutamylfolate + H2O
?
-
longer chain gamma-glutamyl peptides are preferentially attacked by the enzyme
-
-
?
polyglutamylfolate + H2O
?
-
specificity towards analogs of pteroylglutamyl-gamma-glutamyl-gamma-glutamic acid
-
-
?
polyglutamylfolate + H2O
?
-
analogs of the general structure pteroylglutamyl-gamma-glutamyl-gamma-R serve as substrates, low degree of specificity with regard to the nature of the-R group
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme is responsible for the intracellular cleavage of poly-gamma-glutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolylpoly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
key enzyme in the maintenance of cellular folylpolyglutamate concentration
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolyl poly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
folate conjugase in the brush-border may accomplish the initial digestion of the dietary pteroylpolyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
-
-
?
additional information
?
-
-
the maximal velocity decreases in the order methothrexate hexaglutamate, methotrexate tetraglutamate, methotrexate pentaglutamate, methotrexate triglutamate
-
-
?
additional information
?
-
-
soluble enzyme has a requirement for sulfhydryl groups in the active site
-
-
?
additional information
?
-
-
the intracellular enzyme shows the greatest affinity for the complete folic acid molecule with longer glutamate chains
-
-
?
additional information
?
-
-
the intracellular enzyme cleaves both terminal and internal gamma-glutamate linkages, in contrast the brush-border enzyme catalyzes the hydrolysis of only terminal gamma-glutamate linkages
-
-
?
additional information
?
-
-
progressively removes gamma-glutamyl residues at acidic pH from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free gamma-glutamic acid, highly specific for the gamma-glutamyl bond, but not for the C-terminal amino acid (leaving group), action on gamma-glutamyl bonds is independent of an N-terminal pteroyl moiety
-
-
?
additional information
?
-
-
GGH catalyzes degradation of the active polyglutamates of natural folates and the antifolate methotrexate
-
-
?
additional information
?
-
-
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
?
additional information
?
-
the CpG island methylator phenotype in colorectal cancer is defined as concomitant and frequent hypermethylation of CpG islands within gene promoter regions, and is correlated with low expression levels of the enzyme in primary cancer cells, GGH is involved in the folate pathway and in the development and/or progression of this phenotype, CIMP+-related clinicopathological and molecular features, overview
-
-
?
additional information
?
-
-
the enzyme cleaves gamma-polyglutamate chains attached to folates and anti-folates after they enter mammalian cells, the enzyme plays an important role in folate homeostasis and confers resistance to anti-folates, especially methotrexate, the drugs are dependent on polyglutamylation for activity, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
pteroylpolyglutamate + H2O
?
-
the enzyme is responsible for the intracellular cleavage of poly-gamma-glutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolylpoly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
key enzyme in the maintenance of cellular folylpolyglutamate concentration
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolyl poly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
folate conjugase in the brush-border may accomplish the initial digestion of the dietary pteroylpolyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
-
-
?
additional information
?
-
-
GGH catalyzes degradation of the active polyglutamates of natural folates and the antifolate methotrexate
-
-
?
additional information
?
-
-
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
?
additional information
?
-
the CpG island methylator phenotype in colorectal cancer is defined as concomitant and frequent hypermethylation of CpG islands within gene promoter regions, and is correlated with low expression levels of the enzyme in primary cancer cells, GGH is involved in the folate pathway and in the development and/or progression of this phenotype, CIMP+-related clinicopathological and molecular features, overview
-
-
?
additional information
?
-
-
the enzyme cleaves gamma-polyglutamate chains attached to folates and anti-folates after they enter mammalian cells, the enzyme plays an important role in folate homeostasis and confers resistance to anti-folates, especially methotrexate, the drugs are dependent on polyglutamylation for activity, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
p-hydroxymercuribenzoate
-
soluble intracellular enzyme is inhibited, membrane-bound brush-border enzyme not
substituted and reduced pteroylglutamate
-
0.1 mM: not, 30% inhibition at 1.0 mM
iodoacetate
-
inhibition of wild-type enzyme and mutant enzymes C19A, C124A and C290A
additional information
-
no inhibition by diphenylhydantoin or salicylazosulfapyridine; no inhibition by ethanol
-
additional information
-
no inhibition by alpha-diglutamic acid; no inhibition by alpha-triglutamic acid; no inhibition by glutamic acid
-
additional information
-
no inhibition by anionic polysaccharides; no inhibition by pteroic acid; no inhibition by pteroylglutamate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
647293, 647295, 647302, 647305, 647306, 647307, 647308, 647313, 647316, 647317, 647318, 647319, 647320, 668884, 683039, 683179
-
-
two separate folate conjugase activities in jejunal mucosa: one membrane-bound and concentrated in the brush-border and the other soluble and intracellular
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
pulmonary, expression of gamma-glutamyl hydrolase correlates with poor prognosis
primary, low enzyme expression level in cells from the CpG island methylator phenotype, overview
-
gamma-glutamyl hydrolase overexpression decreases global DNA methylation and DNA methyltransferase activity, while gamma-glutamyl hydrolase inhibition increases global DNA methylation and DNA methyltransferase activity. gamma-Glutamyl hydrolase modulation influences CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation
-
gamma-glutamyl hydrolase overexpression decreases global DNA methylation and DNA methyltransferase activity, while gamma-glutamyl hydrolase inhibition increases global DNA methylation and DNA methyltransferase activity. gamma-Glutamyl hydrolase modulation influences CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
the association of -401C/T and +452C/T polymorphisms of gamma-glutamyl hydrolase and the risk of relapse to acute lymphoblastic leukemia is investigated. An association between the -401C/T polymorphism and the risk of relapse is found, patients with the -401T/T genotype have 10.83 more chance of a relapse of leukemia. No association is found between the +452C/T polymorphism and the risk of relapse
physiological function
physiological function
-
gamma-Glutamyl hydrolase modulation-induced changes in total intracellular folate concentrations and content of long-chain folyl-polyglutamates are associated with functionally significant DNA methylation alterations in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation
physiological function
-
overexpression of gamma-glutamyl hydrolase significantly decreases chemosensitivity of MDA-MB-435 cells to 5-fluorouracil and methotrexate at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect is observed only at very high folate concentration, and as the folate concentration decreases this effect becomes null or paradoxically increases. Inhibition of gamma-glutamyl hydrolase significantly increases chemosensitivity of both cancer cells to 5-fluorouracil at all folate concentrations. gamma-Glutamyl hydrolase inhibition significantly decreases chemosensitivity of both cancer cells to methotrexate at all folate concentrations. In both modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increases as folate concentration increases
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). GGH_HUMAN
318
0
35964
Swiss-Prot
Secretory Pathway (Reliability: 1)
A8K335_HUMAN
318
0
36047
TrEMBL
Secretory Pathway (Reliability: 1)
A0A7I2V5X9_HUMAN
271
0
30204
TrEMBL
Secretory Pathway (Reliability: 1)
A0A7I2YQQ3_HUMAN
289
0
32303
TrEMBL
Secretory Pathway (Reliability: 1)
A0A7I2V5P2_HUMAN
245
0
27479
TrEMBL
Secretory Pathway (Reliability: 1)
B4DVI2_HUMAN
205
0
22652
TrEMBL
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
35938
-
2 * 35938, recombinant His-tagged enzyme, dynamic light scattering, analytical ultracentrifugation, and sedimentation velocity measurement, nondissociating homodimer, homodimer formation is required for folding into the active conformation, overview
71880
-
recombinant His-tagged enzyme, dynamic light scattering, analytical ultracentrifugation, and sedimentation velocity measurement
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
2 * 35938, recombinant His-tagged enzyme, dynamic light scattering, analytical ultracentrifugation, and sedimentation velocity measurement, nondissociating homodimer, homodimer formation is required for folding into the active conformation, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
from cancer cells, the enzyme is glycosylated at Asn139, Asn179, partially at Asn283, but not at Asn92
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C124A
-
Km-value for methotrexate diglutamate is not significantly different from the Km-value of the wild-type enzyme. Specific activity is significantly lower than that of the wild-type enzyme, but the mutant protein has a higher amount of contaminating protein
C19A
-
Km-value for methotrexate diglutamate is not significantly different from the Km-value of the wild-type enzyme. Specific activity is significantly lower than that of the wild-type enzyme, but the mutant protein has a higher amount of contaminating protein
C290A
-
Km-value for methotrexate diglutamate is not significantly different from the Km-value of the wild-type enzyme
E222A
-
maximal velocity with methotrexate diglutamate is reduced 6fold relative to the wild-type enzyme
H171N
-
maximal velocity with methotrexate diglutamate is reduced 250fold relative to the wild-type enzyme
T127I
-
distribution of the naturally occuring T127I polymorphism of the enzyme in a Japanese population, genotype distribution and allele frequency, Hardy-Weinberg equilibrium, comparison to Caucasians and in African-Americans populations, overview
additional information
-
the recombinant glycosylated enzyme forms very stable dimeric complexes with the recombinant His-tagged rat enzyme, overview
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged enzyme from Hi5 insect cells, and non-tagged glycosylated enzyme from Hi5 insect cells by anion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression the N-terminally His-tagged and non-tagged glycosylated enzyme in Hi5 insect cells
-
gene GGH, DNA and amino acid sequence determination and analysis, genotyping, overview
-
gene GGH, DNA and amino acid sequence determination and anaylsis, expression analysis, GGH promoter methylation is not a cause of GGH downregulation in CIMP+ colorectal cancer
GGH activity is directly related to GGH messenger RNA expression in acute lymphoblastic leukemia cells of patients with a wild-type germline GGH genotype, identification of two CpG islands, CpG1 and CpG2, in the region extending from the GGH promoter through the first exon and into intron 1, methylation of both CpG islands in the GGH promoter is associated with significantly reduced GGH mRNA expression and catalytic activity and with significantly higher accumulation of MTX polyglutamates in the cells, methylation of CpG1 is leukemia-cell specific and has a pronounced effect on GGH expression, whereas methylation of CpG2 is common in leukemia cells and normal leukocytes but does not significantly alter GGH expression, expression analysis, overview
-
wild-type and mutant enymes C19A, C110A, C124A and C290A are expressed in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
reduced expression of GGH is a predictive factor of a reduced folate level after leucovorin administration in colorectal cancer
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Expression of gamma-glutamyl hydrolase correlates with poor prognosis
medicine
-
genoproteomic mining of urothelial cancer suggests gamma-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy
medicine
the relationships between the reduced folate levels in the colorectal cancer tissue after leucovorin administration and the gene-expression levels of folate-metabolizing enzymes and folate transporters is investigated. A multivariate logistic regression analysis reveals that low gamma-glutamyl hydrolase gene expression is a predictive factor for a high reduced folate level after leucovorin administration
medicine
-
overexpression of gamma-glutamyl hydrolase significantly decreases chemosensitivity of MDA-MB-435 cells to 5-fluorouracil and methotrexate at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect is observed only at very high folate concentration, and as the folate concentration decreases this effect becomes null or paradoxically increases. Inhibition of gamma-glutamyl hydrolase significantly increases chemosensitivity of both cancer cells to 5-fluorouracil at all folate concentrations. gamma-Glutamyl hydrolase inhibition significantly decreases chemosensitivity of both cancer cells to methotrexate at all folate concentrations. In both modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increases as folate concentration increases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baugh, C.M.; Stevens, J.C.; Krumdieck, C.L.
Studies on gamma-glutamyl carboxypeptidase. I. The solid phase synthesis of analogs of polyglutamates of folic acid and their effects on human liver gamma-glutamyl carboxypeptidase
Biochim. Biophys. Acta
212
116-125
1970
Homo sapiens
Lakshmaiah, N.; Ramasastri, B.V.
Plasma folic acid conjugase
Methods Enzymol.
66
670-678
1980
Homo sapiens
Reisenauer, A.M.
Folate conjugase: two separate activities in human jejunum
Science
198
196-197
1977
Homo sapiens
Reisenauer, A.M.; Halsted, C.H.
Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine
Biochim. Biophys. Acta
659
62-69
1981
Homo sapiens
Chandler, C.J.; Wang, T.T.Y.; Halsted, C.H.
Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization
J. Biol. Chem.
261
928-933
1986
Homo sapiens
Lavoie, A.; Tripp, E.; Hoffbrand, A.V.
Sephadex-gel filtration and heat stability of human jejunal and serum pteroylpolyglutamate hydrolase (folate conjugase). Evidence for two different forms
Biochem. Med.
13
1-6
1975
Homo sapiens
Wang, T.T.Y.; Chandler, C.J.; Halsted, C.H.
Intracellular pteroylpolyglutamate hydrolase from human jejunal mucosa. Isolation and characterization
J. Biol. Chem.
261
13551-13555
1986
Homo sapiens
Krungkrai, J.; Yuthavong, Y.; Webster, H.K.
High-performance liquid chromatographic assay for pteroylpolyglutamate hydrolase
J. Chromatogr.
417
47-56
1987
Homo sapiens
Gregory, J.F.3rd.; Ink, S.L.; Cerda, J.J.
Comparison of pteroylpolyglutamate hydrolase (folate conjugase) from porcine and human intestinal brush border membrane
Comp. Biochem. Physiol. B
88
1135-1141
1987
Homo sapiens, Sus scrofa
Jaegerstad, M.; Olsson, I.
Pteroylpolyglutamate hydrolase of human granulocytes. I. Partial purification and kinetic studies
Scand. J. Clin. Lab. Invest.
39
343-349
1979
Homo sapiens
Chave, K.J.; Auger, I.E.; Galivan, J.; Ryan, T.J.
Molecular modeling and site-directed mutagenesis define the catalytic motif in human gamma -glutamyl hydrolase
J. Biol. Chem.
275
40365-40370
2000
Homo sapiens
Galivan, J.; Ryan, T.J.; Chave, K.; Rhee, M.; Yao, R.; Yin, D.
Glutamyl hydrolase: pharmacological role and enzymatic characterization
Pharmacol. Ther.
85
207-215
2000
Homo sapiens
Chave, K.J.; Galivan, J.; Ryan, T.J.
Site-directed mutagenesis establishes cysteine-110 as essential for enzyme activity in human gamma-glutamyl hydrolase
Biochem. J.
343
551-555
1999
Homo sapiens
Rhee, M.S.; Lindau-Shepard, B.; Chave, K.J.; Galivan, J.; Ryan, T.J.
Characterization of human cellular gamma-glutamyl hydrolase
Mol. Pharmacol.
53
1040-1046
1998
Homo sapiens
Li, H.; Ryan, T.J.; Chave, K.J.; Van Roey, P.
Three-dimensional structure of human gamma -glutamyl hydrolase. A class I glatamine amidotransferase adapted for a complex substrate
J. Biol. Chem.
277
24522-24529
2002
Homo sapiens
He, P.; Varticovski, L.; Bowman, E.D.; Fukuoka, J.; Welsh, J.A.; Miura, K.; Jen, J.; Gabrielson, E.; Brambilla, E.; Travis, W.D.; Harris, C.C.
Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray
Hum. Pathol.
35
1196-1209
2004
Homo sapiens
Cheng, Q.; Cheng, C.; Crews, K.R.; Ribeiro, R.C.; Pui, C.H.; Relling, M.V.; Evans, W.E.
Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells
Am. J. Hum. Genet.
79
264-274
2006
Homo sapiens
Eisele, L.E.; Chave, K.J.; Lehning, A.C.; Ryan, T.J.
Characterization of human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer
Biochim. Biophys. Acta
1764
1479-1486
2006
Homo sapiens, Rattus norvegicus (Q62867)
Hayashi, H.; Fujimaki, C.; Inoue, K.; Suzuki, T.; Itoh, K.
Genetic polymorphism of C452T (T127I) in human gamma-glutamyl hydrolase in a Japanese population
Biol. Pharm. Bull.
30
839-841
2007
Homo sapiens
Kawakami, K.; Ooyama, A.; Ruszkiewicz, A.; Jin, M.; Watanabe, G.; Moore, J.; Oka, T.; Iacopetta, B.; Minamoto, T.
Low expression of gamma-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype
Br. J. Cancer
98
1555-1561
2008
Homo sapiens (Q92820)
Schneider, E.; Ryan, T.J.
Gamma-glutamyl hydrolase and drug resistance
Clin. Chim. Acta
374
25-32
2006
Homo sapiens, Mus musculus, Rattus norvegicus
Pollard, C.; Nitz, M.; Baras, A.; Williams, P.; Moskaluk, C.; Theodorescu, D.
Genoproteomic mining of urothelial cancer suggests {gamma}-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy
Am. J. Pathol.
175
1824-1830
2009
Homo sapiens
Sadahiro, S.; Suzuki, T.; Maeda, Y.; Tanaka, A.; Ogoshi, K.; Kamijo, A.; Murayama, C.; Tsukioka, S.; Sakamoto, E.; Fukui, Y.; Oka, T.
Molecular determinants of folate levels after leucovorin administration in colorectal cancer
Cancer Chemother. Pharmacol.
65
735-742
2010
Homo sapiens (Q92820), Homo sapiens
Smit, E.F.; Burgers, S.A.; Biesma, B.; Smit, H.J.; Eppinga, P.; Dingemans, A.M.; Joerger, M.; Schellens, J.H.; Vincent, A.; van Zandwijk, N.; Groen, H.J.
Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer
J. Clin. Oncol.
27
2038-2045
2009
Homo sapiens
Organista-Nava, J.; Gomez-Gomez, Y.; Saavedra-Herrera, M.V.; Rivera-Ramirez, A.B.; Teran-Porcayo, M.A.; Alarcon-Romero, L.d.e.l..C.; Illades-Aguiar, B.; Leyva-Vazquez, M.A.
Polymorphisms of the gamma-glutamyl hydrolase gene and risk of relapse to acute lymphoblastic leukemia in Mexico
Leuk. Res.
34
728-732
2010
Homo sapiens
Kim, S.E.; Cole, P.D.; Cho, R.C.; Ly, A.; Ishiguro, L.; Sohn, K.J.; Croxford, R.; Kamen, B.A.; Kim, Y.I.
gamma-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate
Br. J. Cancer
109
2175-2188
2013
Homo sapiens
Kim, S.E.; Hinoue, T.; Kim, M.S.; Sohn, K.J.; Cho, R.C.; Cole, P.D.; Weisenberger, D.J.; Laird, P.W.; Kim, Y.I.
gamma-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells
Genes Nutr.
10
444
2015
Homo sapiens
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