Information on EC 6.3.2.3 - Glutathione synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
6.3.2.3
-
RECOMMENDED NAME
GeneOntology No.
Glutathione synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid-amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Cysteine and methionine metabolism
-
-
glutathione biosynthesis
-
-
glutathione metabolism
-
-
Glutathione metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
gamma-L-Glutamyl-L-cysteine:glycine ligase (ADP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9023-62-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
indian mustard
-
-
Manually annotated by BRENDA team
Brettanomyces abstinens
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain NBRC13948
-
-
Manually annotated by BRENDA team
strain NBRC13948
-
-
Manually annotated by BRENDA team
recombinant
SwissProt
Manually annotated by BRENDA team
gene gshs1, cv. Jemalong genotype J5
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
isozyme GSHS2, strain 3622
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
cold-adapted, gene gshB
UniProt
Manually annotated by BRENDA team
strain CIAT899
-
-
Manually annotated by BRENDA team
strain CIAT899
-
-
Manually annotated by BRENDA team
Saccharomyces pombe
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain 2603 V/R
UniProt
Manually annotated by BRENDA team
bifucntional glutamate-cysteine ligase and glutathione synthetase
UniProt
Manually annotated by BRENDA team
recombinant
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
metabolism
A485L/T486P mutant shows a shift the substrate specificity increased affinity of GSH2 for Ser as a substrate, while affinity to Gly is preserved. This provides a new biosynthetic pathway for hydroxymethyl glutathione, which is known to be synthesized from glutathione and Ser in a reaction catalysed by carboxypeptidase Y
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + acetyl-Cys + Gly
ADP + phosphate + acetyl-Cys-Gly
show the reaction diagram
-
-
-
-
-
ATP + beta-aminoglutaryl-L-2-aminobutyrate + Gly
ADP + phosphate + beta-aminoglutaryl-L-2-aminobutyryl-Gly
show the reaction diagram
ATP + DL-gamma-(beta-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + DL-gamma-(beta-methyl)Glu-L-2-aminobutyryl-Gly
show the reaction diagram
-
44% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + DL-gamma-(gamma-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + DL-gamma-(gamma-methyl)Glu-L-2-aminobutyryl-Gly
show the reaction diagram
-
16% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + gamma-(alpha-aminomethyl)Glu-2-aminobutyrate + Gly
ADP + phosphate + gamma-Glu-L-2-aminopentanoyl-Gly
show the reaction diagram
-
-
-
-
-
ATP + gamma-Glu-2-aminobutyrate + hydroxylamine
ADP + phosphate + gamma-(alpha-aminomethyl)Glu-2-aminobutyryl-Gly
show the reaction diagram
-
-
-
-
-
ATP + gamma-Glu-aminobutyrate + Gly
ADP + phosphate + ophthalmic acid
show the reaction diagram
ATP + gamma-Glu-L-Cys + Ala
ADP + phosphate + gamma-Glu-Cys-Ala
show the reaction diagram
ATP + gamma-Glu-L-Cys + aminomethanesulfonic acid
ADP + phosphate + gamma-Glu-L-Cys-aminomethanesulfonic acid
show the reaction diagram
Pigeon
-
-
-
-
-
ATP + gamma-Glu-L-Cys + aminooxyacetate
ADP + phosphate + gamma-Glu-Cys-aminoxyacetate
show the reaction diagram
-
53% of the activity relative to Gly
-
-
-
ATP + gamma-Glu-L-Cys + Gly
?
show the reaction diagram
ATP + gamma-Glu-L-Cys + Gly
ADP + phosphate + gamma-glutathione
show the reaction diagram
ATP + gamma-Glu-L-Cys + Gly
ADP + phosphate + glutathione
show the reaction diagram
ATP + gamma-Glu-L-Cys + N-hydroxyglycine
ADP + phosphate + gamma-Glu-Cys-N-hydroxyglycine
show the reaction diagram
-
33% of the activity relative to Gly
-
-
-
ATP + gamma-Glu-L-Cys + Ser
ADP + phosphate + gamma-Glu-Cys-Ser
show the reaction diagram
-
-
-
-
-
ATP + gamma-Glu-S-methylcysteine + Gly
ADP + phosphate + gamma-Glu-S-methylcysteinyl-Gly
show the reaction diagram
ATP + gamma-glutamyl-alpha-aminobutyrate
?
show the reaction diagram
-
-
-
?
ATP + gamma-L-Glu-aminobutanoate + Gly
ADP + phosphate + ophthalmic acid
show the reaction diagram
-
-
-
-
?
ATP + gamma-L-Glu-L-alpha-aminobutyrate + Gly
ADP + phosphate + glutathione
show the reaction diagram
-
-
-
r
ATP + gamma-L-Glu-L-Cys + 3-amino-1-propanol
ADP + phosphate + L-gamma-glutamyl-N-(3-hydroxypropyl)-L-cysteinamide
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + alpha-aminobutyric acid
ADP + phosphate + gamma-Glu-L-Cys-alpha-aminobutyric acid
show the reaction diagram
-
-
-
?
ATP + gamma-L-Glu-L-Cys + beta-Ala
ADP + phosphate + gamma-Glu-L-Cys-beta-Ala
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + beta-Ala
ADP + phosphate + gamma-L-Glu-L-Cys-beta-Ala
show the reaction diagram
no activity with D-Ala
-
-
?
ATP + gamma-L-Glu-L-Cys + beta-aminoisobutyric acid
ADP + phosphate + gamma-Glu-L-Cys-beta-aminoisobutyric acid
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + beta-aminoisobutyric acid
ADP + phosphate + gamma-L-Glu-L-Cys-beta-aminoisobutyric acid
show the reaction diagram
-
-
-
?
ATP + gamma-L-Glu-L-Cys + D-Ala
ADP + phosphate + gamma-Glu-L-Cys-D-Ala
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + D-Ser
ADP + phosphate + gamma-Glu-L-Cys-D-Ser
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + ethanolamine
ADP + phosphate + gamma-Glu-L-Cys-ethanolamine
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + gamma-aminobutyric acid
ADP + phosphate + gamma-Glu-L-Cys-gamma-aminobutyric acid
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + gamma-aminobutyric acid
ADP + phosphate + gamma-L-Glu-L-Cys-gamma-aminobutyric acid
show the reaction diagram
-
-
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + L-2,3-diaminopropionic acid
ADP + phosphate + gamma-Glu-L-Cys-L-2,3-diaminopropionic acid
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + L-2,3-diaminopropionic acid
ADP + phosphate + gamma-L-Glu-L-Cys-L-2,3-diaminopropionic acid
show the reaction diagram
-
-
-
?
ATP + gamma-L-Glu-L-Cys + L-Ala
ADP + phosphate + gamma-Glu-L-Cys-L-Ala
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + L-Ala
ADP + phosphate + gamma-L-Glu-L-Cys-L-Ala
show the reaction diagram
no activity with D-Ala
-
-
?
ATP + gamma-L-Glu-L-Cys + L-Orn
ADP + phosphate + gamma-Glu-L-Cys-L-Orn
show the reaction diagram
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
show the reaction diagram
ATP + Glu-L-2-aminobutyrate + Gly
ADP + phosphate + gamma-Glu-L-Cys-Gly
show the reaction diagram
-
16% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-(alpha-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + L-gamma-(alpha-methyl)Glu-L-2-aminobutyryl-Gly
show the reaction diagram
-
-
-
-
-
ATP + L-gamma-(N-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + L-gamma-(N-methyl)Glu-L-2-aminobutyryl-Gly
show the reaction diagram
-
52% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-Glu-Gly + Gly
ADP + phosphate + L-gamma-Glu-Gly-Gly
show the reaction diagram
-
8% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-Glu-L-2-aminopentanoic acid + Gly
ADP + phosphate + gamma-Glu-S-methylcysteinyl-Gly
show the reaction diagram
-
9% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-Glu-L-Ala + Gly
ADP + phosphate + L-gamma-Glu-L-Ala-Gly
show the reaction diagram
-
55% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-Glu-L-Cys + Gly
ADP + phosphate + L-gamma-Glu-L-Cys-Gly
show the reaction diagram
-
102% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + L-gamma-Glu-L-Ser + Gly
ADP + phosphate + L-gamma-Glu-L-Ser-Gly
show the reaction diagram
-
77% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
ATP + N-acetyl-L-2-aminobutyrate + Gly
ADP + phosphate + N-acetyl-L-2-aminobutyrate-Gly
show the reaction diagram
-
8% of the activity relative to L-gamma-glutamyl-L-2-aminobutyrate
-
-
-
ATP + N-acetyl-L-Cys + Gly
ADP + phosphate + N-acetyl-L-Cys-Gly
show the reaction diagram
-
20% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
-
CTP + gamma-Glu-L-Cys + Gly
CDP + phosphate + glutathione
show the reaction diagram
-
4% of the activity relative to ATP
-
-
-
dATP + gamma-Glu-L-Cys + Gly
dADP + phosphate + glutathione
show the reaction diagram
gamma-L-glutamyl-L-cysteine + glycine + ATP
ADP + phosphate + glutathione
show the reaction diagram
-
-
-
?
glycine + ATP + gamma-L-glutamyl-L-cysteine
ADP + phosphate + glutathione
show the reaction diagram
-
assay at pH 8.2
-
-
?
GTP + gamma-Glu-L-Cys + Gly
GDP + phosphate + glutathione
show the reaction diagram
-
3% of the activity relative to ATP
-
-
-
ITP + gamma-Glu-L-Cys + Gly
IDP + phosphate + glutathione
show the reaction diagram
-
6% of the activity relative to ATP
-
-
-
UTP + gamma-Glu-L-Cys + Gly
UDP + phosphate + glutathione
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
ATP + gamma-Glu-L-Cys + Gly
?
show the reaction diagram
ATP + gamma-Glu-L-Cys + Gly
ADP + phosphate + gamma-glutathione
show the reaction diagram
ATP + gamma-Glu-L-Cys + Gly
ADP + phosphate + glutathione
show the reaction diagram
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
show the reaction diagram
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetate
-
anions that favor activity in decreasing order: acetate, HCOO-, Cl-, at 50 mM K+
Cd2+
-
transgenic plants overexpressing the enzyme from Escherichia coli show enhanced tolerance against cadmium, 3fold in the shoot
Cl-
-
anions that favor activity in decreasing order: acetate, HCOO-, Cl-, at 50 mM K+
HCOO-
-
anions that favor activity in decreasing order: acetate, HCOO-, Cl-, at 50 mM K+
Rb+
-
can replace K+
Zn2+
-
can partially replace Mg2+
additional information
-
transgenic plants overexpressing the enzyme from Escherichia coli show enhanced salt tolerance
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
7,8-dihydrofolate
-
-
adenosine
-
-
adenosine 5'-phosphosulfate
-
slight
adenosine-5'-tetraphospho-5'-pyridoxal
-
when incubated with an adenosine-5'-polyphospho-5'-pyridoxal or pyridoxal phosphate in the presence of Mg2+ and then reduced with sodium borohydride, it is most rapidly inactivated by adenosine-5'-tetraphospho-5'-pyridoxal, addition of either ATP or gamma-glutamylcysteine protects from inactivation
-
Al3+
-
40% residual activity
Ba2+
-
27% residual activity
buthionine sulfoximine
c-jun
AF333982
negative regulation of enzyme expression by blocking the binding of AP-1 to the promotor
-
Chloroquine
-
0.1 mM, 24% inhibition
Co2+
-
complete inhibition
Fe2+
-
2 mM, strong
Fe3+
-
24% residual activity
gamma-(alpha-aminomethyl)Glu-2-aminobutyrate
-
-
gamma-Glu-Cys
-
above 2 mM
glutathione
iodoacetate
L-buthionine-(S,R)-sulfoximine
-
induction of enzyme expression at 0.01 mM
L-cystine
-
1 mM, 11% inhibition
mefloquine
-
0.1 mM, 21% inhibition
menadione
-
wild-type cells are not able to grow on menadione containing substrate, but the recombinant strain is able to survive at 0.1 mM menadione, induction of enzyme expression by superoxide generation
methotrexate
-
-
NADPH
-
weak
Ni2+
-
complete inhibition
p-hydroxymercuribenzoate
-
-
phosphate
tert-butylhydroquinone
AF333982
regulatory role, activator protein 1 AP-1-mediated induction of enzyme expression, 35fold increase in activity in recombinant H4IIE cells, induction of c-jun formation, which is a negative regulatory protein blocking the binding of activator protein 1 to the promotor
trimethoprim
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
activator protein 1
AF333982
i.e. AP-1, mediates the induction of enzyme expression by tert-butylhydroquinone, binds to the enzyme promotor, antagonisted by c-jun, a dominant negative which is also produced in enhanced levels after treatment with tert-butylhydroquinone
-
buthionine sulfoximine
-
increase in enzyme expression in hepatocytes by 2.55fold after 18 h
diethyl maleate
-
increase in enzyme expression in hepatocytes 1.6fold
monocrotaline
-
treatment of rats with monocrotaline, a pyrrolizidine alkaloid, increases the activity of GS
tert-butylhydroquinone
Thioacetamide
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012 - 13.4
ATP
0.32 - 170
beta-Ala
80
gamma-(alpha-aminomethyl)Glu-2-aminobutyrate
-
-
0.22 - 0.5
gamma-Glu-2-aminobutyrate
0.2 - 3.33
gamma-Glu-Cys
0.091
gamma-Glu-L-2-aminobutyrate
-
-
0.03 - 81
gamma-Glu-L-Cys
0.28
gamma-Glu-S-methylcysteine
-
-
0.063
gamma-glutamyl-alpha-aminobutyrate
-
pH 8.2, 37C
0.1 - 1.6
gamma-L-Glu-aminobutanoate
0.042
gamma-L-Glu-L-alpha-aminobutyrate
-
recombinant enzyme, pH 8.2, 37C
0.34 - 8.3
gamma-L-Glu-L-Cys
0.099 - 2
gamma-L-glutamyl-L-cysteine
0.09 - 29.8
Gly
0.07 - 51
glycine
60
N-acetyl-L-2-aminobutyrate
-
-
25
N-acetyl-L-Cys
-
-
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.071 - 55
ATP
0.011 - 55
gamma-Glu-L-Cys
13.6 - 21.7
gamma-L-Glu-aminobutanoate
13
gamma-L-Glu-L-alpha-aminobutyrate
Rattus norvegicus
-
recombinant enzyme, pH 8.2, 37C
0.003 - 6.5
gamma-L-Glu-L-Cys
1.17 - 15.68
gamma-L-glutamyl-L-cysteine
0.052 - 55
Gly
1.17 - 15.68
glycine
additional information
additional information
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.1 - 39.71
ATP
46.63
gamma-L-glutamyl-L-cysteine
Synechocystis sp.
P73493
pH 7.5, 25C, wild-type enzyme
4246
10.36
glycine
Synechocystis sp.
P73493
pH 7.5, 25C, wild-type enzyme
72
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.77 - 2.67
ADP
16.6 - 68.2
glutathione
10.7
GSSG
pH 7.8, 30C, recombinant enzyme
25.1 - 69.1
phosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9
NEM
Setaria cervi
-
IC50: 9 mM, almost complete inhibition at 20 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0006
-
crude extract and cytosolic fraction of leaves
0.0008
-
mitochondrial fraction of leaves
0.0039
-
cell line OC/CDE22, GSH depleted
0.0047
-
cell line M22
0.0064
-
cell line OC/CDE22
0.0078
-
cell line M22, GSH depleted
0.0094
bacteroid isolate
0.0127
-
bacteroid isolate
0.033
-
-
3 - 8
-
about, wild-type mice on minimal diet
11
-
purified recombinant enzyme
17.2
-
purified recombinant wild-type enzyme after complete proteoltic cleavage
17.3
-
purified recombinant isolated subfragments of 24 and 36 kDa
19.3
-
purified recombinant deletion mutant lacking 15 amino acids
20.1
-
purified recombinant wild-type enzyme
21.9
-
purified recombinant enzyme mutant with eliminated cleavage site
29.95
-
pH 8.2, 37C
32
-
about, ApoE-deficient mice on normal diet
33.5
-
about, wild-type mice on normal diet
43
-
about, ApoE-deficient mice on minimal diet
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8.5
-
-
7 - 7.5
-
-
7
-
assay at
7.4 - 8
-
-
8 - 8.5
8
-
assay at
8.5 - 9
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9.7
-
about 50% of maximal activity at pH 7.0 and 9.7
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 30
the recombinant enzyme displays a great temperature-dependent increase in its activity with an unusually high value of energy of activation of 75kJ/mol for a psychrophilic enzyme
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
isozyme GSHS2, isoelectric focusing
5.6 - 5.9
isozyme GSHS2 precursor, isoelectric focusing
6.5
isozyme GSHS1 precursor, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cortical astrocytes
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
ATCC CCL-13, cell culture
Manually annotated by BRENDA team
-
mucosa
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
tumorigenic cell line derived from OC22 by reiterated treatment with N-methyl-N-nitro-N-nitrosoguanidine
Manually annotated by BRENDA team
-
a non-tumorigenic cell line of oval cells established from livers of rats undergoing carcinogenesis by the choline deficient/ethionine-supplemented diet for 12 weeks
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE