6.3.1.2: glutamine synthetase
This is an abbreviated version!
For detailed information about glutamine synthetase, go to the full flat file.
Word Map on EC 6.3.1.2
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6.3.1.2
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aminotransferase
-
gg
-
glial
-
astrocyte
-
nitrate
-
bilirubin
-
sulfoximine
-
alt
-
cerebral
-
hepatocytes
-
retina
-
fibrillary
-
cholesterol
-
glutaminase
-
albumin
-
transaminase
-
creatinine
-
adenylylation
-
triglyceride
-
nodule
-
astroglial
-
bile
-
neurotransmitter
-
excitatory
-
c-reactive
-
uric
-
no3
-
neurotoxicity
-
glutamatergic
-
nitrogenase
-
hyperammonemia
-
excitotoxicity
-
cirrhosis
-
l-methionine
-
anabaena
-
periportal
-
pii
-
cholestasis
-
gamma-gt
-
photorespiratory
-
n2-fixing
-
pericentral
-
gamma-glutamyltransferase
-
photorespiration
-
corpuscular
-
adenylyltransferase
-
drinker
-
assimilatory
-
remobilization
-
drug development
-
synthesis
-
pharmacology
-
diagnostics
-
heterocysts
-
medicine
-
analysis
- 6.3.1.2
- aminotransferase
- gg
- glial
- astrocyte
- nitrate
- bilirubin
- sulfoximine
-
alt
- cerebral
- hepatocytes
- retina
-
fibrillary
- cholesterol
- glutaminase
- albumin
- transaminase
- creatinine
-
adenylylation
- triglyceride
- nodule
-
astroglial
- bile
-
neurotransmitter
-
excitatory
-
c-reactive
-
uric
- no3
-
neurotoxicity
-
glutamatergic
- nitrogenase
-
hyperammonemia
-
excitotoxicity
- cirrhosis
- l-methionine
- anabaena
-
periportal
- pii
- cholestasis
- gamma-gt
-
photorespiratory
-
n2-fixing
-
pericentral
- gamma-glutamyltransferase
-
photorespiration
-
corpuscular
- adenylyltransferase
-
drinker
-
assimilatory
-
remobilization
- drug development
- synthesis
- pharmacology
- diagnostics
- heterocysts
- medicine
- analysis
Reaction
Synonyms
AmGLN1, ATP glutamate-ammonia ligase, Chloroplast GS2, Clone lambda-GS28, Clone lambda-GS31, Clone lambda-GS8, Cytoplasmic GS3, Cytosolic GS1, gamma-glutamyl transferase, gamma-glutamyl:ammonia ligase, gamma-glutamylhydroxamate synthetase, Gln isozyme alpha, Gln isozyme beta, Gln isozyme gamma, Gln synthetase, GLN1,1, GLN1,2, GLN1,3, GLN1,4, GLN1-1, GLN1-2, Gln1;1, Gln1;2, Gln1;3, Gln1;4, Gln1;5, GLN2, GlnA, glnA-1, GlnA1, GlnA2, GlnA3, GlnA4, GlnN, GlnR, GluA, GLUL, Glutamate--ammonia ligase, glutamate-ammonia ligase, Glutamine synthetase, glutamine synthetase cytosolic isozyme 1, glutamine synthetase cytosolic isozyme 2, glutamine synthetase I, glutamine synthetase type II, glutamine synthetase type III, Glutamylhydroxamic synthetase, GS, GS type I, GS type-1, GS(1), GS-II, GS1, GS1 kinase, GS1-1, GS1-2, GS107, GS112, GS117, GS12, GS122, GS1a, GS1beta1, GS1gamma1, GS2, GS2a, GS3, GSI, GSII, GSIII, Isozyme delta, L-glutamate:ammonia ligase, L-glutamate:ammonia ligase (ADP-forming), L-Glutamine synthetase, LDBPK_060370, LdGS, MM_0964, MtGS, N47/N48, OsGLN1,1, OsGLN1,2, protein transacetylase, S2205/S2287, SSO0366, Synthetase, glutamine, TAase, type I glutamine synthetase, type III glutamine synthetase
ECTree
6.3.1.2 glutamine synthetaseAdvanced search results
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results (Inhibitors
Inhibitors on EC 6.3.1.2 - glutamine synthetase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(1R,3R)-1-amino-3-(hydroxy(methyl)phosphoryl)cyclohexane-1-carboxylic acid
-
(1R,3R)-1-amino-3-(hydroxy(methyl)phosphoryl)cyclopentane-1-carboxylic acid
-
(1R,3R)-1-amino-3-(hydroxy(methyl)phosphoryl)cyclopentanecarboxylic acid
-
racemic mixture
(2R)-2-amino-4-(S-methane-N-phosphonosulfonimidoyl)butanoic acid
-
(2S)-2-amino-4-(S-methyl-N-phosphonosulfonimidoyl)butanoic acid
-
-
(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid
docks at the amino acid binding site of the enzyme, structure, overview
(3-methanesulfinylphenylamino)acetic acid
30% inhibition at 1.0 mM
(R)-3-hydroxy-2-(3-sulfamoylphenylamino)propionic acid
33% inhibition at 1.0 mM
(S)-3-hydroxy-2-(3-methanesulfinylphenylamino)propionic acid
13% inhibition at 1.0 mM
([[(2,4-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
-
([[(2,5-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
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1-[(3,4-dichlorophenyl)methyl]-3,7-dimethyl-8-(morpholin-4-yl)-3,7-dihydro-1H-purine-2,6-dione
-
1-[(3,4-dichlorophenyl)methyl]-3,7-dimethyl-8-morpholin-4-yl-purine-2,6-dione
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1-[(3,4-dichlorophenyl)methyl]-8-[(2-methoxyethyl)amino]-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione
-
2-(3-aminophenyl)-6-bromo-N-cyclopentylimidazo[1,2-a]pyridin-3-amine
-
-
2-amino-2-ethyl-4-(S-methylsulfonimidoyl)butanoic acid
-
41% inhibition at 0.4 mM
2-amino-4-(methanesulfinyl)butanoic acid
60% inhibition at 10 mM
2-amino-4-(methanesulfonyl)butanoic acid
78% inhibition at 10 mM
2-amino-4-[(3,4-dichlorobenzyl)(hydroxy)phosphoryl]butanoic acid
-
20% inhibition at 12.5 mM
2-amino-4-[(3,5-dimethylbenzyl)(hydroxy)phosphoryl]butanoic acid
-
20% inhibition at 12.5 mM
2-amino-4-[(4-bromobenzyl)(hydroxy)phosphoryl]butanoic acid
-
20% inhibition at 12.5 mM
2-amino-4-[(aminomethyl)(hydroxy)phosphoryl]butanoic acid
-
2-amino-4-[(carboxymethyl)(hydroxy)phosphoryl]butanoic acid
-
20% inhibition at 12.5 mM
2-amino-4-[hydroxy(phosphonomethyl)amino]butanoic acid
-
50% inhibition at 0.5 mM
2-amino-4-[methyl(phosphonomethyl)amino]butanoic acid
-
29% inhibition at 0.5 mM
2-oxo-2,3-dihydro-1H-benzimidazole-5-sulfonamide
24% inhibition at 1.0 mM
2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-5-phenyl-1H-imidazole
-
-
2-[(1H-benzimidazol-1-yl)methoxy]ethyl diethyl phosphate
competitive versus ATP
2-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyrimidine
-
-
2-[4-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenoxy]acetamide
-
2-[4-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenoxy]ethan-1-ol
-
2-[[4-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenyl](methyl)amino]ethan-1-ol
-
3,4-dichlorophenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
3-[(1H-1,2,4-triazol-3-ylcarbonyl)amino]benzoic acid
26% inhibition at 1.0 mM
3-[4-(6-methoxynaphthalen-2-yl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]phenol
-
-
3-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]benzoic acid
-
3-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenol
-
4-(2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl)pyridin-2-amine
-
-
4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
4-[(oxan-2-yl)oxy]-1-(prop-2-en-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
competitive versus ATP
4-[2-ethyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]-2-fluoropyridine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]-N,N-dimethylpyridin-2-amine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]-N-methylpyridin-2-amine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2(1H)-one
-
-
4-[4-(6-methoxynaphthalen-2-yl)-2-(1H-pyrrol-2-yl)-1H-imidazol-5-yl]pyridine
-
-
4-[4-(6-methoxynaphthalen-2-yl)-2-(2-phenylpropan-2-yl)-1H-imidazol-5-yl]pyridine
-
-
4-[4-(6-methoxynaphthalen-2-yl)-2-(phenoxymethyl)-1H-imidazol-5-yl]pyridine
-
-
4-[4-(6-methoxynaphthalen-2-yl)-2-methyl-1H-imidazol-5-yl]pyridine
-
-
4-[4-(6-methoxynaphthalen-2-yl)-2-phenyl-1H-imidazol-5-yl]pyridine
-
-
5-(2-methoxyethyl)-9-phenyl-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-(3-methylbutyl)-9-(pyridin-3-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-(but-3-en-1-yl)-9-(pyridin-3-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-benzyl-9-phenyl-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-cyclopropyl-9-(pyridin-2-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-methyl-9-phenyl-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-[(3-amino-3-carboxypropyl)(hydroxy)phosphoryl]norvaline
-
20% inhibition at 12.5 mM
5-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyrimidine
-
-
5-[3-(dimethylamino)propyl]-9-(3-methoxyphenyl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-[3-(dimethylamino)propyl]-9-(pyridin-2-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-[3-(dimethylamino)propyl]-9-(pyridin-3-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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5-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]-2-methoxyphenol
-
5-[6-iodo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]-2-methoxyphenol
-
-
6-bromo-N-butyl-2-[4-[2-(dimethylamino)ethoxy]phenyl]imidazo[1,2-a]pyridin-3-amine
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9-(3-chlorophenyl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-(3-methoxyphenyl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-(pyridin-3-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-(quinolin-5-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-bromo-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-phenyl-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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9-phenyl-5-(prop-2-en-1-yl)-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
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alanine
-
more inhibitory for enzyme from strain SA0 than for enzyme from SA1
ascorbate
-
little loss of activity with 2 mM ascorbate alone. Complete inactivation by co-incubation with 1 mM H2O2, 0.002 mM Fe3+, 2 mM ascorbate for 30 min
aspartate
-
more inhibitory for enzyme from strain SA0 than for enzyme from SA1
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate
competitive versus ATP
dithioerythritol
-
no inhibition of wild type enzyme, inhibits activity of D56A and D56E mutant enzymes
Fe3+
-
no loss of activity with 0.002 mM Fe3+ alone. Complete inactivation by co-incubation with 1 mM H2O2, 0.002 mM Fe3+, 2 mM ascorbate for 30 min
L-glutamate
-
in the presence of Mn2+ the activity decreases when exceeding a concentration of 10 mM glutamate
L-methionine-(S)-sulfoximine
docks at the amino acid binding site of the enzyme, structure, overview
L-Tyr
-
inhibits transferase activity, no inhibition of biosynthetic activity
N-(4-hydroxy-3-sulfophenyl)glycine
48% inhibition at 1.0 mM
N-(4-oxo-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-9-yl)acetamide
-
N-Acetylimidazole
inhibition of isozyme MtGS1a; slight inhibition of isozyme MtGS2a
N-[(2S)-2-amino-4-[hydroxy(methyl)phosphoryl]butanoyl]-L-alanyl-L-alanine
-
N-[[(Iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonic acid
-
inactivates Mg2+-dependent activity and activates Mn2+-dependent activity
NaNO3
the specific activity of glutamine synthetase is reduced 66% in the presence of NaNO3
nitrogen sensor protein GlnK1
the nitrogen sensor protein GlnK1 of the methanogenic archaeon interacts and forms stable complexes with glutamine synthetase GlnA1. Complex formation with GlnK1 in the absence of metabolites inhibits the activity of GlnA1. The nitrogen sensor GlnK1 allows finetuning control of the glutamine synthetase activity under changing nitrogen availabilities. The following model is proposed: under nitrogen limitation, increasing concentrations of 2-oxoglutarate stimulate maximal GlnA1 activity and transform GlnA1 into an activated conformation, which prevents inhibition by GlnK1. Upon a shift to nitrogen sufficiency after a period of nitrogen limitation, GlnA1 activity is reduced by decreasing internal 2-oxoglutarate concentrations through diminished direct activation and by GlnK1 inhibition
-
P2X7 receptor
-
stimulation of P2X7 receptors for 2 h inhibits both activity and protein expression of glutamine synthetase, periodate-oxidized 2',3'-dialdehyde ATP abolishes the inhibition
-
S-nitrosoglutathione
isozyme MtGS2a activity is inhibited by thiol residue nitrosylation
serine
-
more inhibitory for enzyme from strain SA0 than for enzyme from SA1
sodium gluconate
the specific activity of glutamine synthetase is reduced 34% in the presence of sodium gluconate
sodium nitroprusside
NO donor sodium nitroprusside results in increased in vivo enzyme nitration accompanied by a reduction in enzyme activity; NO donor sodium nitroprusside results in increased in vivo enzyme nitration accompanied by a reduction in enzyme activity
thymidine
-
complete inhibition of enzyme form GSII, partial inhibition of enzyme form GSI, no effect on enzyme form GSIII
Urea
-
physiological concentrations of urea inhibit, at least when ATP and/or glutamate are nonsaturating. Inhibition is partially reversed by trimethylamine-N-oxide
vitamin D
-
22% inhibition at 0.00001 mM, reduces dexamethasone induced increase in enzyme expression
[(2-chloro-3-methylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
[(3,5-dimethylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
[2-(2,3-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[2-(2,6-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
[2-(2,6-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[2-(3,5-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
[2-(3,5-dimethylphenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[2-(4-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[2-[(5,6,7,8-tetrahydronaphthalen-1-yl)amino]ethane-1,1-diyl]bis(phosphonic acid)
-
[2-[3,5-bis(trifluoromethyl)anilino]ethane-1,1-diyl]bis(phosphonic acid)
-
[3-(diethoxyphosphoryl)phenylamino]acetic acid
42% inhibition at 1.0 mM
[3-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]phenyl]methanol
-
-
[4-(6-methoxynaphthalen-2-yl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]methanol
-
-
[4-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenoxy]acetic acid
-
[[(2,3-dichlorophenyl)amino]methanediyl]bis(phosphonic acid)
non-competitive mechanism against glutamate and uncompetitive mechanism against ATP
[[(2,3-dihydro-1H-inden-5-yl)amino]methylene]bis(phosphonic acid)
-
[[(2,4-dichlorophenyl)amino]methanediyl]bis(phosphonic acid)
non-competitive mechanism against glutamate and uncompetitive mechanism against ATP
[[(2,6-dichlorophenyl)amino]methanediyl]bis(phosphonic acid)
non-competitive mechanism against glutamate and uncompetitive mechanism against ATP
[[(4-chlorophenyl)amino]methanediyl]bis(phosphonic acid)
non-competitive mechanism against glutamate and uncompetitive mechanism against ATP
[[(5,6,7,8-tetrahydronaphthalen-2-yl)amino]methylene]bis(phosphonic acid)
-
[[3-(trifluoromethyl)anilino]methylene]bis(phosphonic acid)
-
(1R,3R)-1-amino-3-(hydroxy(methyl)phosphoryl)cyclohexanecarboxylic acid
-
-
(R)-methionine sulfoximine phosphate
-
weak inhibition compared to the S-enantiomer
(R)-methionine sulfoximine phosphate
weak inhibition compared to the S-enantiomer
(R)-methionine sulfoximine phosphate
-
weak inhibition compared to the S-enantiomer
(R)-methionine sulfoximine phosphate
-
weak inhibition compared to the S-enantiomer
(R)-methionine sulfoximine phosphate
-
weak inhibition compared to the S-enantiomer
(S)-methionine sulfoximine phosphate
-
irreversible, reaction mechanism with required phosphorylation of the inhibitor molecule in the same way as substrate L-glutamate is phosphorylated
(S)-methionine sulfoximine phosphate
irreversible, reaction mechanism with required phosphorylation of the inhibitor molecule in the same way as substrate L-glutamate is phosphorylated
(S)-methionine sulfoximine phosphate
-
irreversible, reaction mechanism with required phosphorylation of the inhibitor molecule in the same way as substrate L-glutamate is phosphorylated
(S)-methionine sulfoximine phosphate
-
irreversible, reaction mechanism with required phosphorylation of the inhibitor molecule in the same way as substrate L-glutamate is phosphorylated
(S)-methionine sulfoximine phosphate
-
irreversible, reaction mechanism with required phosphorylation of the inhibitor molecule in the same way as substrate L-glutamate is phosphorylated
2-amino-2-ethyl-4-[hydroxy(methyl)phosphoryl]butanoic acid
-
2-amino-4-[(phosphonomethyl)sulfonyl]butanoic acid
-
51% inhibition at 0.5 mM
2-mercaptoethanol
-
no inhibition of wild type enzyme, inhibits activity of D56A and D56E mutant enzymes
3-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]benzoic acid
-
-
3-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]benzoic acid
-
3-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]phenol
-
-
3-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]phenol
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2-amine
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2-amine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2-amine
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridine
-
-
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridine
-
5-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]-2-methoxyphenol
-
-
5-[6-bromo-3-(cyclopentylamino)imidazo[1,2-a]pyridin-2-yl]-2-methoxyphenol
-
adenosine
-
more potent inhibitor in the reaction with Mg2+ than with Mn2+
adenosine
-
more potent inhibitor in the reaction with Mg2+ than with Mn2+
adenosine
-
more potent inhibitor in the reaction with Mg2+ than with Mn2+
ADP
-
more potent inhibition in the reaction with Mg2+ than with Mn2+
ADP
competitive inhibitor with respect to ATP and noncompetitive inhibitor versus both glutamate and ammonium
Ala
-
more inhibition by L-Ala and glycine in the mixture with Mn2+ than with Mg2+
Ala
-
more inhibition by L-Ala and glycine in the mixture with Mn2+ than with Mg2+
Ala
-
more inhibition by L-Ala and glycine in the mixture with Mn2+ than with Mg2+
AMP
-
more potent inhibitor in the reaction with Mg2+ than with Mn2+
AMP
-
no feedback inhibition of unadenylated enzyme form, enhanced sensitivity to feedback inhibition by adenylated enzyme form
ATP
-
mutant S186F enzyme is resistant to feedback inhibition by glutamine and AMP
ATP
-
ATP treatment decreases glutamine synthetase activities and protein expression
CTP
-
no feedback inhibition of unadenylated enzyme form, enhanced sensitivity to feedback inhibition by adenylated enzyme form
Cu2+
Cu2+ strongly inhibits the activity of wild-type and mutant enzymes at 1 mM
cysteine
-
no inhibition of wild type enzyme, inhibits activity of D56A and D56E mutant enzymes
cysteine
-
more inhibitory for enzyme from strain SA0 than for enzyme from SA1
glutamate
at high concentrations, isoenzyme GLN1,3
glutamate
-
product inhibition above 20 mM when enzyme is activated with Mg2+, no inhibition when activated with Mn2+
glutamine
-
feed-back inhibition of wild-type enzyme, mutant S186F enzyme is resistant to feedback inhibition
Gly
-
more inhibition by L-Ala and Gly in the mixture with Mn2+ than with Mg2+
Gly
-
more inhibition by L-Ala and Gly in the mixture with Mn2+ than with Mg2+
Gly
-
more inhibition by L-Ala and Gly in the mixture with Mn2+ than with Mg2+
glycine
-
more inhibitory for enzyme from strain SA0 than for enzyme from SA1
H2O2
-
1 mM, 3 h, 63% loss of activity. Inactivation is prevented by the iron chelators 2,2'-dipyridylor 1,10-phenanthroline, but not by their non-chelating analogues
H2O2
-
1 mM, 30 min, 41% loss of activity. Complete inactivation by co-incubation with 1 mM H2O2, 0.002 mM Fe3+, 2 mM ascorbate for 30 min
His
-
no feedback inhibition of unadenylated enzyme form, enhanced sensitivity to feedback inhibition by adenylated enzyme form
L-alanine
feed-back inhibition, competitive with L-glutamine
L-Glu
-
competitive versus L-Gln and non-competitive versus hydroxylamine; gamma-glutamyl transferase activity
L-Glu
-
inhibition of transferase activity, no inhibition of biosynthetic activity
L-glutamine
-
the enzyme is feedback inhibited, the feedback inhibition of GS induces the sequence-specific binding of transcription factor GlnR to DNA in nitrogen metabolism regulation by 32fold and reduces the dissociation rate by 18fold stabilizing the complexes, overview
L-glutamine
feedback inhibition of isozymes GSI-alpha and GSI-beta. Feedback inhibition arises from a hydrogen bond network between Gln, the catalytic glutamate, and the GSI-alpha-specific residue, Arg62, from an adjacent subunit. Arg62 must be ejected for proper active site reorganization. An R62A mutation abrogates Gln feedback inhibition but does not affect catalysis
L-methionine sulfone
-
inhibits enzyme from strain SA0 but not from SA1, more than 80% inhibition at 0.05 mM
L-methionine sulfoximine
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loss of glutamine synthetase activity either inherited or induced through L-methionine sulfoximine leads to an upregulation of the glutamine synthetase protein but not of the glutamine synthetase mRNA and results in a significant drop in the proliferation rate but has no effect on apoptosis
L-methionine sulfoximine
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no inhibition of the acetyltransferase activity
L-methionine sulfoximine
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forward reaction: complete inhibition of wild type enzyme, only slight inhibition of mutant enzyme, reverse reaction: slight inhibition of mutant and wild-type enzyme
L-methionine sulfoximine
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irreversible at high concentrations, competitive with L-Glu; S,R-sulfoximine and S-sulfoximine inhibit, R-sulfoximine is ineffective
L-methionine sulfoximine
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the concentration needed to inhibit GSIII is 50-100times higher than that needed to inhibit GSI or GSII
L-methionine-DL-sulfoximine
MSX, complete inactivation of wild-type and mutant enzymes except D51E mutant, which shows only 10% inhibition
L-methionine-DL-sulfoximine
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inhibits enzyme from strain SA0 but not from SA1, more than 80% inhibition at 0.05 mM
L-phosphinothricin
the glutamine synthetase from Exiguobacterium sp. is L-phosphinothricin resistant. Molecular docking analysis indicates that the substitution of residues Glu60 and Arg64 may lead to significant changes in binding pocket
methionine sulfoximine
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2.5 mM causes up to 60% inhibition of the transferase GS activity and in the presence of 6 mM, the transferase GS activity is around 20% of the controls
methionine sulfoximine
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an irreversible, competitive inhibitor of glutamine synthetase activity
methionine sulfoximine
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treatment with methionine sulfoximine of transgenic mice that overexpresses the mutant human superoxide dismutase SOD1G93A gene, an animalmodel for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis. This treatment in vivo reduces glutamine synthetase activity measured in vitro by 85% and reduces brain levels of glutamine by 60% and of glutamate by 30% in both the motor cortex and the anterior striatum, while also affecting levels of GABA and glutathione. Methionine sulfoxime treatment significantly extends the lifespan of these mice by 8%
methionine sulfoximine
MSO, originally isolated from the maize protein zein after treatment with nitrogen trichloride, targets the amino acid-binding site of the enzyme. Treatment of Mycobacterium tuberculosis with MSO inhibits both cell wall formation and bacterial growth. MSO initially binds as a competitive inhibitor and undergoes rapid phosphorylation by the glutamate synthetase, producing the active form, methionine sulfoximine phosphate (MSO-P). MSO-P binds essentially irreversibly to the active site, preventing entry of the glutamate substrate. The configuration of the two stereocenters is important for inhibitory activity. The (S,S)-diastereomer is 10times more potent than the (S,R)-isomer
methionine sulfoximine
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irreversible inhibition up to 97% in vivo after longterm treatment over 3 h by Intracranial infusion
methionine sulfoximine
competitive inhibitor with respect to L-glutamate
Mg2+
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between 0.5-60 mM, inhibition of Mn2+-dependent transferase activity
Mg2+
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inhibits enzyme form GSIII to nearly 72%, enzyme form GSI 30%, and enzyme form GSII 33.3%
NH4+
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in the presence of Mn2+ the activity decreases when exceeding a concentration of 20 mM NH4+
NH4Cl
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glutamyl transferase reaction, competitive versus L-Gln and non-competitive versus hydroxylamine
Ni2+
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higher affinity for nickel than for the regular co-factor manganese. Upon binding, nickel interferes with the manganese-catalyzed enzymatic activity of recombinant GLUL protein. GLUL activity in testes of animals exposed to nickel sulfate is reduced
nitrogen
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the activity of GlnA1 is downregulated under conditions of nitrogen excess, through covalent binding of an AMP-moiety to a conserved Tyr405 residue by GlnE, an adenylyltransferase
nitrogen
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the activity of GlnA1 is downregulated under conditions of nitrogen excess, through covalent binding of an AMP-moiety to a conserved Tyr405 residue by GlnE, an adenylyltransferase
nitrogen
the activity of GlnA1 is downregulated under conditions of nitrogen excess, through covalent binding of an AMP-moiety to a conserved Tyr405 residue by GlnE, an adenylyltransferase. Both GSII activity and glnII transcription levels increase during nitrogen starvation of morphologically differentiating cultures while there was no change in glnA1 transcription
p-hydroxymercuribenzoate
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complete inhibition of wild type and D56A mutant, 40% inhibition of D56E at 1 mM
Phosphinothricin
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i.e. L-2-amino-4-(hydroxymethyl-phosphinyl)butanoic acid, competitive with respect to Glu, reversible first order inactivation
Phosphinothricin
isolated from Streptomyces viridochromogenes; isolated from Streptomyces viridochromogenes
Phosphinothricin
targets the amino acid-binding site of the enzyme
Phosphinothricin
PPT, complete inactivation of wild-type and mutant enzymes except D51E mutant, which shows 70% inhibition
Trp
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no feedback inhibition of unadenylated enzyme form, enhanced sensitivity to feedback inhibition by adenylated enzyme form
[(3,5-dichloroanilino)methylene]bis(phosphonic acid)
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[[(3,5-dichlorophenyl)amino]methanediyl]bis(phosphonic acid)
non-competitive mechanism against glutamate and uncompetitive mechanism against ATP
additional information
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presence of only one glutathione synthetase inactivation factor, 7A, encoded by open reading frame asl2329, gifA, in strain PCC 7120. Upon addition of ammonium, expression of gifA is derepressed, leading to the synthesis of IF7A, and consequently, glutathione synthetase is inactivated. Upon ammonium removal, the glutathione synthetase activity returns to the initial level and IF7A becomes undetectable. Anabaena glutathione synthetase is not inactivated by Synechocystis IFs. In an Anabaena strain expressing a second inactivating factor, containing the amino-terminal part of IF17 from Synechocystis fused to IF7A, glutathione synthetase inactivation is more effective than that in the wild-ype and resembles that observed in Synechocystis
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
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Bacillus fragilis enzyme produced in E. coli is specifically and irreversibly inactivated by Bacillus fragilis cell extract
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
design and construction of structure-based inhibitors targeting the nucleotide binding site, which varies to a large degree between mammalian and bacterial enzymes
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additional information
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design and construction of structure-based inhibitors targeting the nucleotide binding site, which varies to a large degree between mammalian and bacterial enzymes
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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a single transcriptional repressor AmtR from the TetR family is involved in enzyme regulation, AmtB is encoded by amtB clustered together with glnK in an operon, glnK encodes for a PII signaling protein which are small trimeric proteins that are able to bind 2-oxoglutarate and play a pivotal role in the regulation of nitrogen metabolism by way of controlling the activity of signal transduction components and key metabolic enzymes. GlnK is not uridylylated but rather adenylylated/de-adenylylated by GlnD
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additional information
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inactivation by ADP-ribosylation. The site of ADP-ribosylation is Arg172
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
enzyme inactivation by ferric chloride reagent (0.2 M FeCl3, 0.12 M trichloroacetic acid, and 2.1% concentrated HCl). Enzyme oxidative inactivation by three different metal-catalyzed oxidation (MCO) systems, composed of air, FeCl3 and reducing agents (DTT, ascorbate or GSH), overview; enzyme inactivation by ferric chloride reagent (0.2 M FeCl3, 0.12 M trichloroacetic acid, and 2.1% concentrated HCl). Enzyme oxidative inactivation by three different metal-catalyzed oxidation (MCO) systems, composed of air, FeCl3 and reducing agents (DTT, ascorbate or GSH), overview
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additional information
enzyme inactivation by ferric chloride reagent (0.2 M FeCl3, 0.12 M trichloroacetic acid, and 2.1% concentrated HCl). Enzyme oxidative inactivation by three different metal-catalyzed oxidation (MCO) systems, composed of air, FeCl3 and reducing agents (DTT, ascorbate or GSH), overview; enzyme inactivation by ferric chloride reagent (0.2 M FeCl3, 0.12 M trichloroacetic acid, and 2.1% concentrated HCl). Enzyme oxidative inactivation by three different metal-catalyzed oxidation (MCO) systems, composed of air, FeCl3 and reducing agents (DTT, ascorbate or GSH), overview
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additional information
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the canonical Wnt signalling pathway is a negative regulator of glutamine synthetase activity; the canonical Wnt signalling pathway is a negative regulator of glutamine synthetase activity. No effects by aldosterone, estradiol, progesterone, dihydrotestosterone, or triiodothyronine
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additional information
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elevations in c-jun may be a potential cause of the glutamine synthetase deficiency in mesial temporal lobe epilepsy, MTLE. The activity of glutamine synthetase is decreased by 38% in tissue homogenates of the sclerotic versus the nonsclerotic hippocampus. High levels of c-jun repress the glutamine synthetase gene. The inductive effect of glucocorticoids is mediated by binding of the glucocorticoi receptor to a glucocorticoid response element in the regulatory region of the glutamine synthetase gene, and this effect is blocked by the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha
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additional information
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design and construction of structure-based inhibitors targeting the nucleotide binding site, which varies to a large degree between mammalian and bacterial enzymes
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview; structure-activity relationships and inhibitor design, overview
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additional information
structure-activity relationships and inhibitor design, overview; structure-activity relationships and inhibitor design, overview
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additional information
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combined inhibition by Gly, Ala and Ser is cumulative
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additional information
no inhibition by H2O2 and S-nitrosoglutathione, epicatechin is able to protect isozyme MtGS1a from inactivation; no inhibition by iodoacetamide, epicatechin is not able to protect isozyme MtGS2a from inactivation
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additional information
no inhibition by H2O2 and S-nitrosoglutathione, epicatechin is able to protect isozyme MtGS1a from inactivation; no inhibition by iodoacetamide, epicatechin is not able to protect isozyme MtGS2a from inactivation
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additional information
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no inhibition by H2O2 and S-nitrosoglutathione, epicatechin is able to protect isozyme MtGS1a from inactivation; no inhibition by iodoacetamide, epicatechin is not able to protect isozyme MtGS2a from inactivation
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additional information
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the enzyme is not affeted by dietary glutamine supplementation or by Mycobacterium bovis bacillus Calmette-Guerin infection, overview
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
no inhibition by L-homoserine, (R)-3-hydroxy-2-(3-methanesulfinylphenylamino)propionic acid, (R)-3-hydroxy-2-(3-methylsulfanylphenylamino)propionic acid, (3-sulfamoylphenylamino)acetic acid, (3-methylsulfanylphenylamino)acetic acid, 2-amino-3-(2-phosphonomethylphenyl)propanoic acid, 2-amino-3-(2-aminomethylphenyl)propanoic acid, and methyl 2-amino-3-(2-phosphonomethylphenyl)propanoate, inhibitor screening and docking studies, overview
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additional information
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no inhibition by L-homoserine, (R)-3-hydroxy-2-(3-methanesulfinylphenylamino)propionic acid, (R)-3-hydroxy-2-(3-methylsulfanylphenylamino)propionic acid, (3-sulfamoylphenylamino)acetic acid, (3-methylsulfanylphenylamino)acetic acid, 2-amino-3-(2-phosphonomethylphenyl)propanoic acid, 2-amino-3-(2-aminomethylphenyl)propanoic acid, and methyl 2-amino-3-(2-phosphonomethylphenyl)propanoate, inhibitor screening and docking studies, overview
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additional information
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a single transcriptional repressor AmtR from the TetR family is involved in enzyme regulation, AmtB is encoded by amtB clustered together with glnK in an operon, glnK encodes for a PII signaling protein which are small trimeric proteins that are able to bind 2-oxoglutarate and play a pivotal role in the regulation of nitrogen metabolism by way of controlling the activity of signal transduction components and key metabolic enzymes. GlnK is not uridylylated but rather adenylylated/de-adenylylated by GlnD
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
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synthesis and inhibitory potency of 2-tert-butyl-4,5-diarylimidazoles inhibitors, overview. No inhibition by 4-[4-(6-methoxynaphthalen-2-yl)-2-(phenoxymethyl)-1H-imidazol-5-yl]pyridine and [4-(6-methoxynaphthalen-2-yl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]methanol
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additional information
high throughput screening of series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones as enzyme inhibitors, overview. None of these compounds is active on whole cell Mycobacterium tuberculosis. Structure activity relationships of 5,10-dihydro-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one derivatives
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additional information
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high throughput screening of series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones as enzyme inhibitors, overview. None of these compounds is active on whole cell Mycobacterium tuberculosis. Structure activity relationships of 5,10-dihydro-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one derivatives
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additional information
43 bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, are synthesized and screened against recombinant enzyme from Mycobacterium tuberculosis. Some of the inhibitors are much more effective against the pathogen enzyme than against the human orthologue. Bone-targeting properties of the bisphosphonate compounds. No inhibition by [(3,5-dibromoanilino)methylene]bis(phosphonic acid), [[3,5-bis(trifluoromethyl)anilino]methylene]bis(phosphonic acid), (anilinomethylene)di(lambda5-phosphanedione), [(4-methylanilino)methylene]di(lambda5-phosphanedione), [(3,5-dichloroanilino)methylene]di(lambda5-phosphanedione), and [(4-benzylanilino)methylene]di(lambda5-phosphanedione). Molecular modeling
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additional information
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43 bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, are synthesized and screened against recombinant enzyme from Mycobacterium tuberculosis. Some of the inhibitors are much more effective against the pathogen enzyme than against the human orthologue. Bone-targeting properties of the bisphosphonate compounds. No inhibition by [(3,5-dibromoanilino)methylene]bis(phosphonic acid), [[3,5-bis(trifluoromethyl)anilino]methylene]bis(phosphonic acid), (anilinomethylene)di(lambda5-phosphanedione), [(4-methylanilino)methylene]di(lambda5-phosphanedione), [(3,5-dichloroanilino)methylene]di(lambda5-phosphanedione), and [(4-benzylanilino)methylene]di(lambda5-phosphanedione). Molecular modeling
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additional information
in contrast to methionine sulfoximine, MSO, the sulfone and sulfoxide analogues are weak, reversible enzyme inhibitors. Poor or no inhibition by 2-amino-4-(ethanesulfonyl)butanoic acid and amino[3-(methanesulfonyl)phenyl]acetic acid
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additional information
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in contrast to methionine sulfoximine, MSO, the sulfone and sulfoxide analogues are weak, reversible enzyme inhibitors. Poor or no inhibition by 2-amino-4-(ethanesulfonyl)butanoic acid and amino[3-(methanesulfonyl)phenyl]acetic acid
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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3'-O-(4-benzoylbenzoyl)-ATP suppresses the enzyme expression. Removal of extracellular Ca2+ and inhibition of protein kinase C restores the ATP-decreased enzyme expression but fails to restore the P2X7-decreased L-glutamate uptake
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additional information
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inhibitory effects of endothelins on the expression of glutamine synthetase, cultured cortical astrocytes maintained with endothelins show an almost complete loss of glutamine synthetase, this coordinated inhibition of astroglial glutamate uptake and turnover, e.g. by ET-1, dissociates when extracellular glutamate concentrations increase, overview
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
Sorghum sp.
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
GlnR is able to function as both an activator and repressor of transcription
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additional information
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GlnR is able to function as both an activator and repressor of transcription
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additional information
no effect with L-histidine or L-tryptophane
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additional information
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no effect with L-histidine or L-tryptophane
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additional information
structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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additional information
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structure-activity relationships and inhibitor design, overview
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