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 hide
3.4.19.9
-
RECOMMENDED NAME
GeneOntology No.
gamma-glutamyl hydrolase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
hydrolysis of a gamma-glutamyl bond
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
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
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9074-87-7
not distinguishable from EC 3.4.17.11 in Chemical Abstracts
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
NBRC16449, CMU29, isolated from Thai Thua-nao, a natto-like fermented soybean food
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
AB strain
UniProt
Manually annotated by BRENDA team
Micromonospora melanosporea
IFO 12515, 2 poly(glutamic acid) hydrolases: PGH-I and PGH-II
-
-
Manually annotated by BRENDA team
TM-4222
-
-
Manually annotated by BRENDA team
TM-4222
-
-
Manually annotated by BRENDA team
Ailsa Craig
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
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
-
-
-
-
?
5,10-methenyltetrahydrofolate glutamate + H2O
5,10-methenyltetrahydrofolate + L-glutamate
show the reaction diagram
-
-
-
?
5,10-methenyltetrahydrofolate heptaglutamate + 7 H2O
5,10-methenyltetrahydrofolate + 7 L-glutamate
show the reaction diagram
-
-
-
?
5,10-methenyltetrahydrofolate hexaglutamate + 6 H2O
5,10-methenyltetrahydrofolate + 6 L-glutamate
show the reaction diagram
-
-
-
?
5-formyltetrahydrofolate glutamate + H2O
5-formyltetrahydrofolate + L-glutamate
show the reaction diagram
-
-
-
?
5-formyltetrahydrofolate heptaglutamate + 7 H2O
5-formyltetrahydrofolate + 7 L-glutamate
show the reaction diagram
-
-
-
?
5-formyltetrahydrofolate hexaglutamate + 6 H2O
5-formyltetrahydrofolate + 6 L-glutamate
show the reaction diagram
-
-
-
?
5-formyltetrahydrofolate triglutamate + H2O
?
show the reaction diagram
5-L-glutamyl-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate glutamate + H2O
5-methyltetrahydrofolate + L-glutamate
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate heptaglutamate + 7 H2O
5-methyltetrahydrofolate + 7 L-glutamate
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate hexaglutamate + 6 H2O
5-methyltetrahydrofolate + 6 L-glutamate
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
PteGlu5
-
-
?
glutamyl-gamma-glutamate + H2O
glutamate
show the reaction diagram
-
-
-
-
?
glutathione + H2O
?
show the reaction diagram
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 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 glutamate + tetraglutamate
show the reaction diagram
-
-
-
?
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
-
-
-
-
?
methotrexate triglutamate + H2O
methotrexate monoglutamate + methotrexate diglutamate + glutamate
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
p-aminobenzoylpentaglutamate + H2O
?
show the reaction diagram
pABAGlu5
-
-
?
poly-Glu + H2O
?
show the reaction diagram
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
polyglutamylfolate + H2O
?
show the reaction diagram
pteroyl-penta-gamma-glutamate + H2O
?
show the reaction diagram
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
pteroylhexaglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroylpentaglutamate + H2O
?
show the reaction diagram
pteroylpolyglutamate + H2O
?
show the reaction diagram
pteroyltetraglutamate + H2O
?
show the reaction diagram
-
-
-
-
?
pteroyltriglutamate + H2O
?
show the reaction diagram
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
show the reaction diagram
tetra-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
tri-gamma-L-glutamate + H2O
L-glutamate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
-
-
?
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
-
-
?
p-aminobenzoylpentaglutamate + H2O
?
show the reaction diagram
B2Z9Y3, B2Z9Y4, B2Z9Y5
pABAGlu5
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
show the reaction diagram
pteroylpolyglutamate + H2O
?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
slight activation
Fe2+
-
slight activation
Na+
-
stimulates
Ni2+
-
slight activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-hydroxymercuribenzoate
6-diazo-5-oxo-norleucine
-
-
acivicin
-
-
azaserine
-
-
Cd2+
-
-
citrate
-
-
Concanavalin
-
-
-
Dextran sulfate
DNA
-
-
Fe3+
-
-
gamma-diglutamate
-
-
heparin
Hg2+
-
-
iodoacetate
Mn2+
-
-
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-Hydroxymercuriphenylsulfonate
-
-
Phenylmethylsulfonylfluoride
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
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
p-hydroxymercuribenzoate
-
slightly enhances activity
sulfhydryl compounds
-
activate
Urea
-
low concentrations stimulate
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.057
5-formyltetrahydrofolate triglutamate
Vmax: 87.6 nmol/min/microg
0.0076
5-L-glutamyl-4-nitroanilide
-
pH 7.8, 52C
0.0012 - 0.00138
folic acid pentaglutamate
0.0076
L-glutamic acid gamma-(4-nitroanilide)
-
Vmax: 0.36 micromol/min/mg
0.0214 - 0.049
methotrexate diglutamate
0.00083
N5-methyltetrahydropteroyltetraglutamate
-
-
0.00098 - 0.00186
p-aminobenzoylpentaglutamate
0.0006
pteroyldiglutamate
-
-
0.00021 - 0.0006
Pteroylheptaglutamate
0.00052 - 0.00079
pteroylpentaglutamate
6
pteroyltetraglutamate
-
-
0.00055 - 0.0287
Pteroyltriglutamate
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
48.2
5-formyltetrahydrofolate triglutamate
Danio rerio
Q6NY42
Vmax: 87.6 nmol/min/microg
1.69 - 2.13
folic acid pentaglutamate
0.96 - 8.29
p-aminobenzoylpentaglutamate
0.04 - 19.46
pteroylpentaglutamate
additional information
additional information
Bos taurus
-
pteroyltriglutamate: 732 gamma-glutamyl bonds are cleaved per min per mol of enzyme
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.9
-
sodium acetate buffer
4 - 4.5
-
-
4.1
-
2 pH-optima: pH 4.1 and pH 5.2
4.5
-
sodium citrate buffer
4.5 - 6
-
-
4.5 - 5
-
and a second optimum at pH 6.7-7.5, bile
5.1
-
pteroyltetraglutamate
5.2
-
2 pH-optima: pH 4.1 and pH 5.2
6 - 6.5
-
-
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
10
Micromonospora melanosporea
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
LITERATURE
25
-
assay at
50
Micromonospora melanosporea
-
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
about 25% of activity maximum at 30C and 80C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
six-day-old
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
and all other organs; and all other organs
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
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21000
-
SDS-PAGE, shorter subunit after post-translational modification
29000
-
-
32000
Micromonospora melanosporea
-
gel filtration
36300
calculated from sequence
36400
calculated from sequence
36700
calculated from sequence
44000
-
gel filtration
45000
-
soluble intracellular enzyme, gel filtration
55000
-
gel filtration
57500
-
gel filtration
61000
-
SDS-PAGE, precursor homotetrameric protein of 61000 Da per subunit
68000
-
gel filtration
71880
-
recombinant His-tagged enzyme, dynamic light scattering, analytical ultracentrifugation, and sedimentation velocity measurement
75000
-
human, gel filtration
83000
-
enzyme from jejunum
91000
-
membrane-bound enzyme, gel filtration
103000
-
gel filtration
108000
-
gel filtration
110000
222000
-
gel filtration
700000
-
gel filtration
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
the homodimer is catalytically inactive
heterotetramer
-
2 * 21000, 2 * 40000, SDS-PAGE
homodimer
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 hide
LITERATURE
glycoprotein
proteolytic modification
-
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; 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
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to 1.9 A resolution. A zinc-binding motif, His-Glu-His, is present at the C-terminal end of the beta-sheet. The enzyme has a catalytic center containing a zinc ion and an overall topology resembling mammalian carboxypeptidase A and related enzymes
wild-type and mutants C108A and H218N in complex with substrate methotrexate pentaglutamate and product methotrexate glutamate, to 1.9 to 2.4 A resolution. The side chain of residue Phe20 and the 6-methylpterin ring of methotrexate pentaglutamate invoke pi-pi interactions to promote distinct concerted conformational alterations involving about 90 rotations in the complexes with the C108A and H218N mutant proteins
hanging-drop vapor diffusion method, crystal structure at 1.6-A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
LITERATURE
37
-
unstable at pH 4.5, protective effect of the substrate
45
-
24 h, 83% residual activity; pH 7.8, GthGT retains 83% of the activity after 24 h incubation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
2-mercaptoethanol is required for stabilization
-
stability against various dialysis procedures
-
substrate protects
-
unaffected by dialysis against 1 mM EDTA
-
zinc is essential for stability
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, partially purified enzyme is stable for 3 months
-
4C, 5.0 mM 2-mercaptoethanol, 40% loss of activity after 24 h
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography
after induction with isopropyl thiogalactoside, the enzyme is purified with a Ni-Sepharose column
baculovirus-expressed enzyme
-
H35 hepatoma cells
-
native enzyme from culture broth
-
partial
PGH-II
Micromonospora melanosporea
-
recombinant AtGGH1; recombinant AtGGH2
recombinant enzyme expressed in Escherichia coli
-
recombinant His-tagged enzyme from Hi5 cells to homogeneity
recombinant N-terminally His-tagged enzyme from Hi5 insect cells, and non-tagged glycosylated enzyme from Hi5 insect cells by anion exchange chromatography
-
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
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AtGGH1 is expressed in truncated form in Escherichia coli; AtGGH2 is expressed in truncated form in Escherichia coli
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)
expressed as a fusion protein containing a C-terminal His-tag in Escherichia coli; expression in Escherichia coli
-
expression in Escherichia coli
expression of N-terminally His-tagged enzyme in Hi5 insect cells
expression the N-terminally His-tagged and non-tagged glycosylated enzyme in Hi5 insect cells
-
expression with a baculovirus/Sf9 insect cell expression system
-
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
-
overexpression in MCF7 breast cancer cells and HT1080 fibrosarcoma cells
-
the gene localizes to chromosome 4 under control of two distinct promoters
-
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
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E165A
mutant shows no poly-gamma-glutamate hydrolysis activity
E45A
mutant shows no poly-gamma-glutamate hydrolysis activity
H103A
mutant shows no poly-gamma-glutamate hydrolysis activity
H40A
mutant shows no poly-gamma-glutamate hydrolysis activity
H78A
mutant shows no poly-gamma-glutamate hydrolysis activity
C108A
complete loss of hydrolytic activity
F20A
about 40% decrease in hyrolytic activity
F20A/C108A
complete loss of hydrolytic activity
F20R
about 40% increase in hyrolytic activity
F20R/C108A
complete loss of hydrolytic activity
H218N
complete loss of hydrolytic activity. Residue His218 alone suffices to catalyze the hydrolysis of the gamma-glutamate bond in gamma-glutamyl hydrolase
T353A
-
mutation abolishes the post-translational cleavage of the pro-enzyme, but does not completely block the hydrolytic action; 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
C110A
-
inactive mutant enzyme
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
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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
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
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