Information on EC 3.4.19.9 - gamma-glutamyl hydrolase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
3.4.19.9
-
RECOMMENDED NAME
GeneOntology No.
gamma-glutamyl hydrolase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of a gamma-glutamyl bond
show the reaction diagram
-
-
-
-
hydrolysis of a gamma-glutamyl bond
show the reaction diagram
catalytic mechanism, the enzyme releases mono- or di-glutamate
-
hydrolysis of a gamma-glutamyl bond
show the reaction diagram
Tyr36 is catalytically essential
-
hydrolysis of a gamma-glutamyl bond
show the reaction diagram
Tyr36 is catalytically essential
Q62867
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
4-hydroxy-2-nonenal detoxification
-
-
Folate biosynthesis
-
-
glutamate removal from folates
-
-
glutathione metabolism
-
-
glutathione-mediated detoxification I
-
-
glutathione-mediated detoxification II
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxypeptidase G
-
-
-
-
conjugase
-
-
-
-
FGPH
-
-
-
-
folate conjugase
-
-
-
-
folic acid conjugase
-
-
-
-
folylpolyglutamate hydrolase
-
-
-
-
gamma-Glu-X carboxypeptidase
-
-
-
-
gamma-glutamyl hydrolase
-
-
-
-
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
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9074-87-7
not distinguishable from EC 3.4.17.11 in Chemical Abstracts
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
NBRC16449, CMU29, isolated from Thai Thua-nao, a natto-like fermented soybean food
-
-
Manually annotated by BRENDA team
AB strain
UniProt
Manually annotated by BRENDA team
Danio rerio AB
AB strain
UniProt
Manually annotated by BRENDA team
Japanese healthy individuals
-
-
Manually annotated by BRENDA team
patients with chronic myeloid leukemia
-
-
Manually annotated by BRENDA team
single gene and single spliced mRNA
-
-
Manually annotated by BRENDA team
two separate folate conjugase activities in jejunal mucosa: one membrane-bound and concentrated in the brush-border and the other soluble and intracellular
-
-
Manually annotated by BRENDA team
Micromonospora melanosporea
IFO 12515, 2 poly(glutamic acid) hydrolases: PGH-I and PGH-II
-
-
Manually annotated by BRENDA team
Myrothecium sp.
TM-4222
-
-
Manually annotated by BRENDA team
Myrothecium sp. TM-4222
TM-4222
-
-
Manually annotated by BRENDA team
cv. Homesteader
-
-
Manually annotated by BRENDA team
gene Ggh
SwissProt
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(4,4-difluoro)glutamyl-gamma-glutamate + H2O
(4,4-difluoro)glutamate + glutamate
show the reaction diagram
-
the fluorine substitution results in a significant decrease in rates of hydrolysis under steady-state conditions due primarily to a 15fold increase in Km compared to the unsubstituted substrate
-
-
?
(poly-gamma-glutamate)n + H2O
(poly-gamma-glutamate)n-1 + glutamate
show the reaction diagram
-
-
-
-
?
(poly-gamma-L-glutamate)n + H2O
oligo-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
2,4-diamino-10-methyl-pteroylglutamyl-gamma-glutamate + H2O
2,4-diamino-10-methyl-pteroate + glutamate + gamma-glutamylglutamate
show the reaction diagram
-
-
bile enzyme at a ratio of 5:95 and plasma enzyme at a ratio of 23:77
?
2,4-diamino-10-methyl-pteroylglutamyl-gamma-glutamate + H2O
2,4-diamino-10-methyl-pteroate + glutamate + gamma-glutamylglutamate
show the reaction diagram
-
-
bile enzyme at a ratio of 5:95 and plasma enzyme at a ratio of 23:77
?
4-aminobenzoyl-(4,4-difluoro)glutamyl-gamma-glutamate + H2O
4-aminobenzoyl-(4,4-difluoro)glutamate + glutamate
show the reaction diagram
-
the fluorine substitution results in a significant decrease in rates of hydrolysis under steady-state conditions due primarily to a 15fold increase in Km compared to the unsubstituted substrate
-
-
?
4-aminobenzoyl-gamma-Glu + H2O
4-aminobenzoate + Glu
show the reaction diagram
-
-
-
-
?
4-aminobenzoyl-gamma-Glu-gamma-Glu-Tyr + H2O
?
show the reaction diagram
-
-
-
-
?
4-aminobenzoyl-penta-gamma-glutamate + H2O
4-aminobenzoylglutamate + tetra-gamma-glutamate
show the reaction diagram
-
-
subsequently degraded to glutamic acid
?
4-aminobenzoyltriglutamate + H2O
?
show the reaction diagram
-
at 13% the rate of pteroyltriglutamate hydrolysis
-
-
?
4-hydroxy-2-nonenal-glutathione conjugate + H2O
4-hydroxy-2-nonenal-[Cys-Gly] conjugate + L-glutamate
show the reaction diagram
-
-
-
-
?
5,10-dideazatetrahydrofolate + H2O
?
show the reaction diagram
-
-
-
-
?
5-formyltetrahydrofolate triglutamate + H2O
?
show the reaction diagram
Danio rerio, Danio rerio AB
Q6NY42
-
-
-
?
5-L-glutamyl-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
di-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
folate + H2O
pteroate + glutamate
show the reaction diagram
-
-
-
-
?
folic acid pentaglutamate + H2O
?
show the reaction diagram
B2Z9Y3, B2Z9Y4, B2Z9Y5
PteGlu5
-
-
?
glutamyl-gamma-glutamate + H2O
glutamate
show the reaction diagram
-
-
-
-
?
glutathione + H2O
?
show the reaction diagram
-
enzyme hydrolyses the physiological antioxidant glutathione, suggesting an involvement of the enzyme in the cellular defense mechanism against oxidative stress
-
-
?
L-glutamic acid gamma-(4-nitroanilide) + H2O
L-glutamic acid + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
methotrexate + H2O
?
show the reaction diagram
-
-
-
-
?
methotrexate diglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
methotrexate diglutamate + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
methotrexate hexaglutamate + H2O
methotrexate pentaglutamate + methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate
show the reaction diagram
-
-
-
?
methotrexate penta-gamma-glutamate + H2O
methotrexate-gamma-glutamate + tetra-gamma-glutamate
show the reaction diagram
-
-
subsequently degraded to glutamic acid
?
methotrexate pentaglutamate + H2O
methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate + L-glutamate
show the reaction diagram
-
-
-
?
methotrexate polyglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
methotrexate tetraglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
N5-methyltetrahydropteroyltetraglutamate + H2O
?
show the reaction diagram
-
cleaves the terminal gamma-glutamyl residues, finally releasing a monoglutamyl end-product
-
-
?
oligo-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
p-aminobenzoyl-penta-gamma-glutamate + H2O
?
show the reaction diagram
O65355
AtGGH1 cleaves pentaglutamates mainly to di- and triglutamates, AtGGH2 cleaves pentaglutamates mainly to monoglutamates
-
-
?
p-aminobenzoylpentaglutamate + H2O
?
show the reaction diagram
B2Z9Y3, B2Z9Y4, B2Z9Y5
pABAGlu5
-
-
?
poly-Glu + H2O
?
show the reaction diagram
Micromonospora melanosporea
-
-
Glu-Glu + oligomers of Glu
?
poly-Glu + H2O
?
show the reaction diagram
Myrothecium sp., Myrothecium sp. TM-4222
-
enzyme is specific for poly(gamma-glutamic) acid, but not for other gamma-glutamyl peptides or amides
endo-type specificity, 38% of the original poly-Glu with an average MW of 500000 is converted to smaller peptides, and then depolymerized to a mixture of gamma-oligopeptides which consist of only L-glutamic acid, L-glutamic acid monomer is negligible in the reaction mixture, the remaining 62% of poly(gamma-glutamic acid) are resistant to the enzyme action
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
Q62867
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
gamma-glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary folate in rat small intestine
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
removal of the poly-gamma-glutamate chains
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
Q62867
removal of the poly-gamma-glutamate chains
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
-
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
sequential hydrolysis of glutamates with the dissociation of substrate from enzymic surface following cleavage of each glutamate seems likely
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
bond cleavage occurs with equal facility at internal points of the peptide chain
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
longer chain gamma-glutamyl peptides are preferentially attacked by the enzyme
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
longer chain gamma-glutamyl peptides are preferentially attacked by the enzyme, peptide bond cleavage occurs only at gamma-glutamyl bonds and the presence of a COOH-terminal gamma bond is essential for enzyme action, the cleavage of diglutamyl peptides is extremely slow, the cleavage of gamma bonds is independent of the NH2-terminal pteroyl moiety
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
specificity towards analogs of pteroylglutamyl-gamma-glutamyl-gamma-glutamic acid
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
enzyme from mouse kidney shows mixed endo- and exopeptidase activity, the enzyme from all other normal tissues and tumor cells is consistent with endopeptidase activity
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
endo/random hydrolysis of gamma-glutamyl peptide bonds of pteroylpolyglutamate substrates yielding folic acid as the terminal product
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
endopeptidase-like mode of action
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
endopeptidase-like mode of action
-
-
?
polyglutamylfolate + H2O
?
show the reaction diagram
-
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
-
-
?
pteroyl-penta-gamma-glutamate + H2O
?
show the reaction diagram
O65355
AtGGH1 cleaves pentaglutamates mainly to di- and triglutamates, AtGGH2 cleaves pentaglutamates mainly monoglutamates
-
-
?
pteroyldiglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylglutamylhexaglutamate + H2O
short-chain pteroylglutamates
show the reaction diagram
-
-
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
?
pteroylheptaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylheptaglutamate + H2O
?
show the reaction diagram
-
-
pteroyldiglutamate + gamma-Glu5
?
pteroylheptaglutamate + H2O
?
show the reaction diagram
-
-
pteroylmonoglutamate + hexaglutamyl peptide
?
pteroylhexaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpentaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpentaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpentaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpentaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme is responsible for the intracellular cleavage of poly-gamma-glutamates
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
pancreatic enzyme may act in vivo in folate digestion and absorption to initiate the deconjugation of dietary pteroylpolyglutamate prior to the action of jejunal brush-border enzyme
-
-
-
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
central enzyme in folyl and antifolylpoly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
key enzyme in the maintenance of cellular folylpolyglutamate concentration
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
central enzyme in folyl and antifolyl poly-gamma-glutamate metabolism
-
-
-
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
folate conjugase in the brush-border may accomplish the initial digestion of the dietary pteroylpolyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
possible contribution of biliary enzyme to intestinal absorption of folate polyglutamates
-
-
?
pteroyltetraglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
-
-
+ pteroyldiglutamate
?
tetra-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
tri-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
methotrexate triglutamate + H2O
methotrexate monoglutamate + methotrexate diglutamate + glutamate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the maximal velocity decreases in the order methothrexate hexaglutamate, methotrexate tetraglutamate, methotrexate pentaglutamate, methotrexate triglutamate
-
-
-
additional information
?
-
-
endopeptidase activity, no hydrolysis of poly-alpha-glutamate
-
-
-
additional information
?
-
-
no hydrolysis of gamma-glutamyl tripeptide
-
-
-
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
?
-
-
protein-associated poly-gamma-glutamates are poor substrates, no hydrolysis of 4-amino-benzoyl-gamma-glutamate
-
-
-
additional information
?
-
-
the enzyme is a cysteine peptidase
-
-
-
additional information
?
-
-
no hydrolysis of alpha-glutamyl peptides
-
-
-
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
?
-
-
no hydrolysis of N-carbobenzoxyphenylalanyl-alanine
-
-
-
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
?
-
Q62867
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
-
additional information
?
-
Q92820
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
-
-
-
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
-
-
-
additional information
?
-
-
the enzyme specifically cleaves D- and L-polyglutamic acid, preferred to entirely of poly-D-glutamic acid, a component of the capsule produced by several strains of Bacillus subtilis, the enzyme has minimal activity in degrading Bacillus anthracis and to remove the capsule from the surface of bacilli, the poly-gamma-D-glutamic acid capsule, no effect on RAW264.7 murine macrophage phagocytosis, and only minimal enhancement of human host neutrophil killing
-
-
-
additional information
?
-
-
either deacylation or rearrangement of the enzyme-product complex is rate-limiting in the isopeptide hydrolysis reaction
-
-
-
additional information
?
-
-
the enzyme hydrolyzes synthetically hydrolyzed oligo-gamma-L-glutamates, but not oligo-gamma-D-glutamates, and degrades polyglutamic acid to a hydrolyzed product of about 20 kDa with a ratio of D- and L-glutamic acids of 70:30, thus the enzyme cleaves the bond between two L-glutamic acid residues, overview
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
-
additional information
?
-
Q6NY42
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
-
additional information
?
-
-
enzyme does not show any transpeptidase activity
-
-
-
additional information
?
-
Danio rerio AB
Q6NY42
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
folate + H2O
pteroate + glutamate
show the reaction diagram
-
-
-
-
?
folic acid pentaglutamate + H2O
?
show the reaction diagram
B2Z9Y3, B2Z9Y4, B2Z9Y5
PteGlu5
-
-
?
p-aminobenzoylpentaglutamate + H2O
?
show the reaction diagram
B2Z9Y3, B2Z9Y4, B2Z9Y5
pABAGlu5
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
Q62867
-
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
-
gamma-glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary folate in rat small intestine
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme is responsible for the intracellular cleavage of poly-gamma-glutamates
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
pancreatic enzyme may act in vivo in folate digestion and absorption to initiate the deconjugation of dietary pteroylpolyglutamate prior to the action of jejunal brush-border enzyme
-
-
-
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
central enzyme in folyl and antifolylpoly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
key enzyme in the maintenance of cellular folylpolyglutamate concentration
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
central enzyme in folyl and antifolyl poly-gamma-glutamate metabolism
-
-
-
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
folate conjugase in the brush-border may accomplish the initial digestion of the dietary pteroylpolyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
the enzyme progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
-
-
?
pteroylpolyglutamate + H2O
?
show the reaction diagram
-
possible contribution of biliary enzyme to intestinal absorption of folate polyglutamates
-
-
?
glutathione + H2O
?
show the reaction diagram
-
enzyme hydrolyses the physiological antioxidant glutathione, suggesting an involvement of the enzyme in the cellular defense mechanism against oxidative stress
-
-
?
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
?
-
Q62867
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
-
additional information
?
-
Q92820
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
-
-
-
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
-
-
-
additional information
?
-
-
the enzyme specifically cleaves D- and L-polyglutamic acid, preferred to entirely of poly-D-glutamic acid, a component of the capsule produced by several strains of Bacillus subtilis, the enzyme has minimal activity in degrading Bacillus anthracis and to remove the capsule from the surface of bacilli, the poly-gamma-D-glutamic acid capsule, no effect on RAW264.7 murine macrophage phagocytosis, and only minimal enhancement of human host neutrophil killing
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
-
additional information
?
-
B2Z9Y3, B2Z9Y4, B2Z9Y5
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
-
additional information
?
-
Danio rerio, Danio rerio AB
Q6NY42
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
activation; slight activation
Ca2+
-
activation
Cd2+
-
slight activation
Fe2+
-
slight activation
Mg2+
-
activation; slight activation
Mg2+
-
activation
Mn2+
-
stimulates
Mn2+
-
activation; slight activation
Mn2+
-
activation
Na+
-
stimulates
Ni2+
-
slight activation
Zinc
-
contains 4.15-4.47 zinc atoms per molecule of enzyme
Zinc
-
Zn2+ stimulates
Zn2+
-
Zn2+ or Mn2+ are required
Mn2+
-
Zn2+ or Mn2+ are required
additional information
-
in cationic buffers, the enzyme has a higher activity than in anionic buffers of the same ionic strength and pH
additional information
-
Ca2+, Co2+, Mg2+, Mn2+, and Ni2+ at 5 mM have little effect on enzyme activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-hydroxymercuribenzoate
-
40% inhibition at 5 mM
4-hydroxymercuribenzoate
-
-
6-Diazo-5-oxo-norleucine
-
-
acivicin
-
-
azaserine
-
-
Cd2+
-
-
citrate
-
-
Concanavalin
-
-
-
Cu2+
-
-
Cu2+
Micromonospora melanosporea
-
-
Cu2+
Myrothecium sp.
-
weak
Dextran sulfate
-
-
-
Dextran sulfate
-
-
-
DNA
-
-
EDTA
Micromonospora melanosporea
-
-
EDTA
Myrothecium sp.
-
no inhibition
Fe3+
-
-
gamma-diglutamate
-
-
heparin
-
-
heparin
-
no inhibition
Hg2+
-
-
iodoacetate
-
-
iodoacetate
-
inhibition of wild-type enzyme and mutant enzymes C19A, C124A and C290A
NEM
-
-
Ni2+
Micromonospora melanosporea
-
-
o-phenanthroline
Micromonospora melanosporea
-
-
p-Aminobenzoate
-
0.1 mM: no inhibition, 30% inhibition at 1.0 mM
p-Aminobenzoylglutamate
-
slight
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
soluble intracellular enzyme is inhibited, membrane-bound brush-border enzyme not
p-hydroxymercuribenzoate
-
-
p-Hydroxymercuriphenylsulfonate
-
-
PCMB
-
-
PCMB
Micromonospora melanosporea
-
-
PCMB
Myrothecium sp.
-
-
Phenylmethylsulfonylfluoride
-
-
Phenylmethylsulfonylfluoride
Myrothecium sp.
-
no inhibition
poly-gamma-glutamic acid
-
-
Pterine
-
-
pteroyldiglutamate
-
hydrolysis of pteroyltriglutamate
Pteroylheptaglutamate
-
hydrolysis of pteroyltriglutamate
pteroylpentaglutamate
-
hydrolysis of pteroyltriglutamate
RNA
-
-
Salicylazosulfapyridine
-
-
substituted and reduced pteroylglutamate
-
0.1 mM: not, 30% inhibition at 1.0 mM
Zn2+
-
bile enzyme inhibited at pH 7.5 but not at pH 4.5
Zn2+
-
0.1 mM zinc acetate, weak
Mn2+
-
-
additional information
Micromonospora melanosporea
-
no inhibition by diisopropylfluorophosphate
-
additional information
-
no inhibition by 2-mercaptomethylglutaric acid
-
additional information
Myrothecium sp.
-
no inhibition by competitive inhibitors of serine and cysteine proteinases; no inhibition by phosphoramidon
-
additional information
-
the active centre is not blocked by thiol reagents or fluorophosphates
-
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
-
additional information
-
no inhibition by EDTA, PMSF, or iodoacetic acid at 5 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
stimulates
2-mercaptoethanol
-
stimulates
p-hydroxymercuribenzoate
-
slightly enhances activity
sulfhydryl compounds
-
activate
Urea
-
low concentrations stimulate
2-mercaptoethanol
-
-
additional information
-
erythromycin slightly stimulates the enzyme-mediated phagocytosis
-
additional information
-
preincubation of the enzyme at 25 C for 2 h is necessary to obtain maximal activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.057
5-formyltetrahydrofolate triglutamate
Q6NY42
Vmax: 87.6 nmol/min/microg
0.0076
5-L-glutamyl-4-nitroanilide
-
pH 7.8, 52C
0.0012
folic acid pentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
-
0.00138
folic acid pentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
-
0.0076
L-glutamic acid gamma-(4-nitroanilide)
-
Vmax: 0.36 micromol/min/mg
0.0214
methotrexate diglutamate
-
mutant enzyme E222A
0.0222
methotrexate diglutamate
-
mutant enzyme C19A
0.0231
methotrexate diglutamate
-
mutant enzyme C290A
0.02945
methotrexate diglutamate
-
wild-type enzyme
0.0299
methotrexate diglutamate
-
mutant enzyme H171N
0.0303
methotrexate diglutamate
-
mutant enzyme C124A
0.00083
N5-methyltetrahydropteroyltetraglutamate
-
-
0.00098
p-aminobenzoylpentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
0.00131
p-aminobenzoylpentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
0.0015
p-aminobenzoylpentaglutamate
O65355
37C, pH 6.0, AtGGH1
0.00186
p-aminobenzoylpentaglutamate
O65355
37C, pH 6.0, AtGGH2
0.0006
pteroyldiglutamate
-
-
0.00021
Pteroylheptaglutamate
-
-
0.0006
Pteroylheptaglutamate
-
-
0.00052
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH2
0.00079
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH1
6
pteroyltetraglutamate
-
-
0.00055
Pteroyltriglutamate
-
-
0.00067
Pteroyltriglutamate
-
-
0.0012
Pteroyltriglutamate
-
-
0.0016
Pteroyltriglutamate
-
-
0.0017
Pteroyltriglutamate
-
-
0.0091
Pteroyltriglutamate
-
-
0.024
Pteroyltriglutamate
-
-
0.0287
Pteroyltriglutamate
-
pH 4.0
0.049
methotrexate diglutamate
-
wild-type enzyme
additional information
additional information
-
Km of methotrexate polyglutamates
-
additional information
additional information
-
Michaelis-Menten kinetics, detailed steady-state kinetics and partial pre-steady-state kinetics, stopped-flow method, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
48.2
5-formyltetrahydrofolate triglutamate
Q6NY42
Vmax: 87.6 nmol/min/microg
1.69
folic acid pentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
-
0.96
p-aminobenzoylpentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
1.08
p-aminobenzoylpentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
5.51
p-aminobenzoylpentaglutamate
O65355
37C, pH 6.0, AtGGH2
8.29
p-aminobenzoylpentaglutamate
O65355
37C, pH 6.0, AtGGH1
0.04 - 1.97
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH2
1.1
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH1
8.74
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH2
19.46
pteroylpentaglutamate
O65355
37C, pH 6.0, AtGGH1
2.13
folic acid pentaglutamate
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
-
additional information
additional information
-
pteroyltriglutamate: 732 gamma-glutamyl bonds are cleaved per min per mol of enzyme
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
Myrothecium sp.
-
-
additional information
-
-
additional information
-
HPLC assay
additional information
-
assay using pteroyl-labeled substrates and selective short-term bacterial uptake for product determination
additional information
-
-
additional information
-
highest activity in the postprandial duodenal luminal fluid at pH 4.5
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.9
-
sodium acetate buffer
4 - 4.5
-
-
4.1
-
2 pH-optima: pH 4.1 and pH 5.2
4.5 - 5
-
and a second optimum at pH 6.7-7.5, bile
4.5 - 6
-
-
4.5
-
sodium citrate buffer
4.5
-
soluble intracellular enzyme
5
Myrothecium sp.
-
-
5.1
-
pteroyltetraglutamate
5.2
-
2 pH-optima: pH 4.1 and pH 5.2
6 - 6.5
-
-
6
-
hydrolysis of pteroyltriglutamate and pteroylpentaglutamate
6
-
assay at
6.2 - 7.5
-
plasma
6.7 - 7.5
-
and a second optimum at pH 4.5-5.0, bile
7.5
-
brush-border enzyme
7.8
Myrothecium sp.
-
-
7.8
-
assay at
10
Micromonospora melanosporea
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 7
-
about 45% of activity maximum at pH 4 and pH 7
4.5 - 6.5
-
4.5 is the pH optimum, while pH 6.5 is the in vivo reaction temperature
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
37
Myrothecium sp.
-
-
37
-
assay at
37
-
assay at
50
Micromonospora melanosporea
-
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
about 25% of activity maximum at 30C and 80C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary, low enzyme expression level in cells from the CpG island methylator phenotype, overview
Manually annotated by BRENDA team
Myrothecium sp.
-
-
Manually annotated by BRENDA team
Myrothecium sp. TM-4222
-
-
-
Manually annotated by BRENDA team
-
of H35 hepatoma cells
Manually annotated by BRENDA team
-
high activity at pH 4.5
Manually annotated by BRENDA team
B2Z9Y3, B2Z9Y4, B2Z9Y5
-
Manually annotated by BRENDA team
-
and all other organs
Manually annotated by BRENDA team
-
mucosal brush-border
Manually annotated by BRENDA team
-
brush-border membrane vesicles
Manually annotated by BRENDA team
-
enzyme expression in mucosa
Manually annotated by BRENDA team
-
enzyme expression
Manually annotated by BRENDA team
-
neuroendocrine tumor cell
Manually annotated by BRENDA team
-
duodenal, jejunal, and ileal mucosa
Manually annotated by BRENDA team
-
pulmonary, expression of gamma-glutamyl hydrolase correlates with poor prognosis
Manually annotated by BRENDA team
-
enzyme expression
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
-
SDS-PAGE, shorter subunit after post-translational modification
702486
29000
-
-
647312
32000
Micromonospora melanosporea
-
gel filtration
647297
36300
B2Z9Y3, B2Z9Y4, B2Z9Y5
calculated from sequence
694732
36400
B2Z9Y3, B2Z9Y4, B2Z9Y5
calculated from sequence
694732
36700
B2Z9Y3, B2Z9Y4, B2Z9Y5
calculated from sequence
694732
39000
B2Z9Y3, B2Z9Y4, B2Z9Y5
SDS-PAGE
694732
40000
B2Z9Y3, B2Z9Y4, B2Z9Y5
SDS-PAGE
694732
40000
-
SDS-PAGE, shorter subunit after post-translational modification
702486
42000
B2Z9Y3, B2Z9Y4, B2Z9Y5
SDS-PAGE
694732
44000
-
gel filtration
702486
45000
-
soluble intracellular enzyme, gel filtration
647296
55000
-
gel filtration
647298
57500
-
gel filtration
647290
61000
-
SDS-PAGE, precursor homotetrameric protein of 61000 Da per subunit
702486
68000
Myrothecium sp.
-
gel filtration
647300
71880
-
recombinant His-tagged enzyme, dynamic light scattering, analytical ultracentrifugation, and sedimentation velocity measurement
683179
75000
-
human, gel filtration
647307
80000
-
gel filtration
647292
80000
-
-
647310
83000
-
enzyme from jejunum
647306
91000
-
membrane-bound enzyme, gel filtration
647296
103000
-
gel filtration
702486
108000
-
gel filtration
647294
110000
-
gel filtration
647295
110000
-
enzyme from serum
647306
222000
-
gel filtration
702486
700000
-
gel filtration
647305
additional information
-
the enzyme shows 2 peaks on gel filtration: MW 50000 Da and 25000 Da
647311
additional information
-
MW of detergent enzyme complexes: above 500000 Da
647313
additional information
-
MW of detergent enzyme complexes: 227000 Da
647313
additional information
Q6NY42
recombinant NH-zgammaGH and zgammaGH appear on SDS-PAGE in the ranges of their estimated size of 92 and 33 kDa, respectively
692046
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 28000, SDS-PAGE
?
-
x * 37000, SDS-PAGE
?
-
x * 145000 + x * 115000, SDS/urea PAGE
dimer
-
1 * 43000 + 1 * 18000, SDS-PAGE of 2-mercaptoethanol treated enzyme, the 2 disulfide-linked polypeptide chains are independently active
dimer
O65355
AtGGH1, AtGGH2
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
dimer
-
homodimer with a very large monomer-momoner interface
dimer
Q62867
nondissociating homodimer, homodimer formation is required for folding into the active conformation, overview
heterodimer
B2Z9Y3, B2Z9Y4, B2Z9Y5
the homodimer is catalytically inactive
heterotetramer
-
2 * 21000, 2 * 40000, SDS-PAGE
homodimer
Q6NY42
zgammaGH. NH-zgammaGH is a tetramer. It seems that the presence of the N-terminal Nus and His-tag interferes with the quaternary structure of zgammaGH
homodimer
Danio rerio AB
-
zgammaGH. NH-zgammaGH is a tetramer. It seems that the presence of the N-terminal Nus and His-tag interferes with the quaternary structure of zgammaGH
-
homotetramer
-
4 * 61000 Da, SDS-PAGE
tetramer
-
2 * 40000 + 2 * 21000, SDS-PAGE. The unprocessed enzyme forms an already active homotetramer, whereas the mature enzyme is a fully active compact alpha2beta2-heterotetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
-
proteolytic modification
-
the enzyme is synthesized as a precursor homotetrameric protein of 60 kDa per subunit, and undergoes an internal post-translational cleavage of the 60 kDa monomer into 40 kDa and 21 kDa shorter subunits, which are then assembled into an active heterotetramer composed of two 40 kDa and two 21 kDa subunits, precursor homotetrameric protein of 61000 Da per subunit undergoes an internal post-translational cleavage into 40 and 21 kDa shorter subunits, which are then assembled into an active heterotetramer composed of two 40 and two 21 kDa subunits
glycoprotein
-
-
glycoprotein
-
from cancer cells, the enzyme is glycosylated at Asn139, Asn179, partially at Asn283, but not at Asn92
glycoprotein
-
from cancer cells
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor diffusion method, crystal structure at 1.6-A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 10
Micromonospora melanosporea
-
40C, 60 min, stable
647297
6.5
-
stable at pH 6.5 and above, 90 min
647305
7
-
maximal stability
647312
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
unstable at pH 4.5, protective effect of the substrate
647307
40
Micromonospora melanosporea
-
pH 4.0-10.0, 60 min, stable
647297
40
Myrothecium sp.
-
stable up to, 1 h, pH 5.0
647300
40
-
1 h, pH 8.0, stable
683268
45
-
24 h, 83% residual activity; pH 7.8, GthGT retains 83% of the activity after 24 h incubation
702486
50
Micromonospora melanosporea
-
below, pH 9.0, 15 min, stable
647297
50
-
jejunal enzyme stable, serum enzyme inactivated
647306
65
-
little thermal denaturation below
647294
65
-
up to, for at least 90 min
647305
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stability against various dialysis procedures
-
zinc is essential for stability
-
2-mercaptoethanol is required for stabilization
-
substrate protects
-
unaffected by dialysis against 1 mM EDTA
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 5.0 mM 2-mercaptoethanol, 40% loss of activity after 24 h
-
-70C, partially purified enzyme is stable for 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant AtGGH1; recombinant AtGGH2
O65355
native enzyme from culture broth
-
after induction with isopropyl thiogalactoside, the enzyme is purified with a Ni-Sepharose column
Q6NY42
affinity chromatography
-
partial
-
using Ni-NTA chromatography
-
baculovirus-expressed enzyme
-
recombinant enzyme expressed in Escherichia coli
-
recombinant N-terminally His-tagged enzyme from Hi5 insect cells, and non-tagged glycosylated enzyme from Hi5 insect cells by anion exchange chromatography
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PGH-II
Micromonospora melanosporea
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Myrothecium sp.
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partial
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affinity chromatography
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H35 hepatoma cells
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recombinant His-tagged enzyme from Hi5 cells to homogeneity
Q62867
recombinant proteins are purified by Ni2+ affinity chromatography; recombinant proteins are purified by Ni2+ affinity chromatography; recombinant proteins are purified by Ni2+ affinity chromatography; in the case of LeGGH1, an additional cation exchange step is required
B2Z9Y3, B2Z9Y4, B2Z9Y5
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AtGGH1 is expressed in truncated form in Escherichia coli; AtGGH2 is expressed in truncated form in Escherichia coli
O65355
cloned and inserted into a pET43.1a vector via SmaI and EcoRI sites and expressed in Rosetta (DE3) cells as a Nus-His-tag fusion enzyme (NH-zgammaGH)
Q6NY42
expressed as a fusion protein containing a C-terminal His-tag in Escherichia coli; expression in Escherichia coli
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expression the N-terminally His-tagged and non-tagged glycosylated enzyme in Hi5 insect cells
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expression with a baculovirus/Sf9 insect cell expression system
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gene GGH, DNA and amino acid sequence determination and analysis, genotyping, overview
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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
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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
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overexpression in MCF7 breast cancer cells and HT1080 fibrosarcoma cells
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wild-type and mutant enymes C19A, C110A, C124A and C290A are expressed in Escherichia coli
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the gene localizes to chromosome 4 under control of two distinct promoters
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expression of N-terminally His-tagged enzyme in Hi5 insect cells
Q62867
when coexpressed in Escherichia coli, homodimer is catalytically inactive. LeGGH3 forms heterodimers with LeGGH1 or LeGGH2 that has one-half the activity of the matching homodimer; when coexpressed in Escherichia coli, LeGGH1 forms heterodimers with an intermediate bond cleavage preference; when coexpressed in Escherichia coli, LeGGH2 forms heterodimers with an intermediate bond cleavage preference
B2Z9Y3, B2Z9Y4, B2Z9Y5
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
reduced expression of GGH is a predictive factor of a reduced folate level after leucovorin administration in colorectal cancer
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T353A
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mutation of the N-terminal residue of the 21 kDa subunit, abolishes the post-translational cleavage of the pro-enzyme, but does not completely block the hydrolytic action, mutation abolishes the post-translational cleavage of the pro-enzyme, but does not completely block the hydrolytic action
C110A
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inactive mutant enzyme
C124A
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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
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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
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Km-value for methotrexate diglutamate is not significantly different from the Km-value of the wild-type enzyme
E222A
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maximal velocity with methotrexate diglutamate is reduced 6fold relative to the wild-type enzyme
H171N
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maximal velocity with methotrexate diglutamate is reduced 250fold relative to the wild-type enzyme
H220A
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inactive mutant enzyme
H220N
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site-directed mutagenesis, inactive mutant
additional information
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the recombinant glycosylated enzyme forms very stable dimeric complexes with the recombinant His-tagged rat enzyme, overview
T127I
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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
Q62867
the enzyme forms very stable dimeric complexes with the glycosylated human enzyme, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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trienzyme extraction is a combined enzymatic digestion by Pronase, alpha-amylase, and conjugase, i.e. gamma-glutamyl hydrolase, to liberate the carbohydrate and protein-bound folates from food matrices prior to total folate analysis by microbiological assay using Lactobacillus casei ssp. rhamnosus, ATCC 7469, determine the contribution of the enzymes to the growth response, the extraction method is used in AOAC Official Method 2004.05 for the folate analysis of cereal foods
medicine
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gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Expression of gamma-glutamyl hydrolase correlates with poor prognosis
medicine
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genoproteomic mining of urothelial cancer suggests gamma-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy
medicine
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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