2.6.1.19: 4-aminobutyrate-2-oxoglutarate transaminase
This is an abbreviated version!
For detailed information about 4-aminobutyrate-2-oxoglutarate transaminase, go to the full flat file.
Word Map on EC 2.6.1.19
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2.6.1.19
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gabaergic
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neurotransmitter
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seizure
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epilepsy
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anticonvulsant
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agonist
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antiepileptic
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aminooxyacetic
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gamma-vinyl
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dopamine
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bicuculline
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muscimol
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shunt
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hypothalamus
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neurotransmission
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pyridoxal
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gabab
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convulsion
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valproate
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gabaculine
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excitatory
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baclofen
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striatum
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benzodiazepine
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transmitter
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synaptosomes
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diazepam
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transamination
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ssadh
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gaba-mediated
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substantia
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picrotoxin
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neurochemical
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tiagabine
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pentylenetetrazol
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3hgaba
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3-mercaptopropionic
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4.1.1.15
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homocarnosine
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gamma-hydroxybutyrate
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silverman
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nipecotic
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gabapentin
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plp-dependent
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kindling
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electroshock
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enzyme-activated
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clonic
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gaba-induced
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ethosuximide
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medicine
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molecular biology
- 2.6.1.19
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gabaergic
-
neurotransmitter
- seizure
- epilepsy
-
anticonvulsant
- agonist
-
antiepileptic
-
aminooxyacetic
-
gamma-vinyl
- dopamine
- bicuculline
- muscimol
-
shunt
- hypothalamus
-
neurotransmission
- pyridoxal
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gabab
- convulsion
- valproate
- gabaculine
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excitatory
- baclofen
- striatum
- benzodiazepine
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transmitter
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synaptosomes
- diazepam
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transamination
- ssadh
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gaba-mediated
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substantia
- picrotoxin
-
neurochemical
-
tiagabine
-
pentylenetetrazol
-
3hgaba
-
3-mercaptopropionic
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4.1.1.15
- homocarnosine
- gamma-hydroxybutyrate
-
silverman
-
nipecotic
- gabapentin
-
plp-dependent
-
kindling
-
electroshock
-
enzyme-activated
-
clonic
-
gaba-induced
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ethosuximide
- medicine
- molecular biology
Reaction
Synonyms
4-aminobutyrate aminotransferase, 4-aminobutyrate transaminase, 4-aminobutyrate-2-ketoglutarate aminotransferase, 4-aminobutyrate-2-oxoglutarate aminotransferase, 4-aminobutyrate-2-oxoglutarate transaminase, 4-aminobutyric acid 2-ketoglutaric acid aminotransferase, 4-aminobutyric acid aminotransferase, ABAT, aminobutyrate aminotransferase, aminobutyrate transaminase, aminotransferase, aminobutyrate, argD, argD6803, argD7002, Atu3000, beta-alanine aminotransferase, beta-alanine transaminase, beta-alanine-oxoglutarate aminotransferase, beta-alanine-oxoglutarate transaminase, bioA, CG010_026395, CgGABA-AT, GABA aminotransferase, GABA transaminase, GABA transferase, GABA-2-oxoglutarate aminotransferase, GABA-2-oxoglutarate transaminase, GABA-alpha-ketoglutarate aminotransferase, GABA-alpha-ketoglutarate transaminase, GABA-alpha-ketoglutaric acid transaminase, GABA-alpha-oxoglutarate aminotransferase, GABA-AT, GABA-oxoglutarate aminotransferase, GABA-oxoglutarate transaminase, GABA-T, GABA-T1, GABA-T2, GABA-T3, GABA-TA, GABA-transaminase, GABA:2-oxoglutarate aminotransferase, GABAT, GabT, gamma-aminobutyrate aminotransaminase, gamma-aminobutyrate aminotransferase, gamma-aminobutyrate transaminase, gamma-aminobutyrate transaminases, gamma-aminobutyrate-alpha-ketoglutarate aminotransferase, gamma-aminobutyrate-alpha-ketoglutarate transaminase, gamma-aminobutyrate: GABA transaminase, gamma-aminobutyrate:alpha-oxoglutarate aminotransferase, gamma-aminobutyric acid aminotransferase, gamma-aminobutyric acid pyruvate transaminase, gamma-aminobutyric acid transaminase, gamma-aminobutyric acid-2-oxoglutarate transaminase, gamma-aminobutyric acid-alpha-ketoglutarate transaminase, gamma-aminobutyric acid-alpha-ketoglutaric acid aminotransferase, gamma-aminobutyric transaminase, gatT, glutamate-succinic semialdehyde transaminase, homotaurine:2-oxoglutarate aminotransferase, MdGABA-T1, MdGABA-T2, More, NCgl0462, NCgl2515, Osl2, pollen-pistil incompatibility 2, Pop2, SkUga1p, slr1022
ECTree
2.6.1.19 4-aminobutyrate-2-oxoglutarate transaminaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 2.6.1.19 - 4-aminobutyrate-2-oxoglutarate transaminase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(+/-)-(1S,2R,4S,5S)-4-amino-6,6-difluorobicyclo[3.1.0]hexane-2-carboxylic acid
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10 mM, weak, reversible inhibitor
(+/-)-(1S,2S,4S,5S)-4-amino-6,6-difluorobicyclo[3.1.0]hexane-2-carboxylic acid
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10 mM, weak, reversible inhibitor
(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid
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mechanism-based inactivation, adduct formed is derived from enamine mechanism
(1R,4S)-4-amino-2-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
(1R,4S)-4-amino-3-fluorocyclopent-2-enecarboxylic acid
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weak reversible inhibition in the presence of beta-mercaptoethanol
(1R,4S)-4-amino-3-pentafluoroethylcyclopent-2-enecarboxylic acid
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weak reversible inhibition in the presence of beta-mercaptoethanol
(1R,4S)-4-amino-3-trifluoromethylcyclopent-2-enecarboxylic acid
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irreversible inhibition in the presence of beta-mercaptoethanol
(1S,2S,3E)-2-amino-3-(fluoromethylidene)cyclopentanecarboxylic acid
monofluorinated analog of inhibitor CPP-115. Compound produces a metabolite that induces disruption of the Glu270-Arg445 salt bridge of GABA transaminase to accommodate interaction between the metabolite formyl group and Arg445. The inactivation mechanism is initiated by Schiff base formation with the active site pyridoxal 5'-phosphate, followed by gamma-proton removal
(1S,2S,3Z)-2-amino-3-(fluoromethylidene)cyclopentanecarboxylic acid
monofluorinated analog of inhibitor CPP-115. Compound produces a metabolite that induces disruption of the Glu270-Arg445 salt bridge of GABA transaminase to accommodate interaction between the metabolite formyl group and Arg445. The inactivation mechanism is initiated by Schiff base formation with the active site pyridoxal 5'-phosphate, followed by gamma-proton removal
(1S,3S)-(Z)-3-amino-4-(2,2,2-trifluoroethylidene)cyclopentanecarboxylic acid
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inhibition in the presence of beta-mercaptoethanol
(1S,3S)-3-amino-4-(2,2,2-trifluoro-1-trifluoromethylethylidene)-cyclopentanecarboxylic acid
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weak reversible inhibition in the presence of beta-mercaptoethanol
(1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid
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potent irreversible inhibitor
(1S,4R)-4-amino-2-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
(1S,4S)-2-(difluoromethylidene)-4-(1H-tetrazol-5-yl)cyclopentanamine
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time-dependent inactivation, ratio kinact/KI value at pH 8.0 is 2.48 per min and mM
(2E)-4-methylpentan-2-one N-(2,4-dimethylphenyl)semicarbazone
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57% inhibition at 0.125 mM
(2E)-butan-2-one N-(2,4-dimethylphenyl)semicarbazone
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89% inhibition at 0.0625 mM
(4R)-4-amino-1-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
(4S)-4-amino-1-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
(R,S)-4-amino-3-fluorobutanoic acid
the (R)-enantiomer inhibits the transamination of gamma-aminobutanoic acid 10 times more effectively than the (S)-enantiomer. On binding of free 4-amino-3-fluorobutanoic acid to enzyme the optimal conformation places the C-NH3 + and C-F bonds gauche in the (R)-enantiomer but anti in the (S)-enantiomer
(S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid
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mechanism-based inactivator, reacts via aromatization mechanism
2,4-dimethylphenyl semicarbazide hydrochloride
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90% inhibition at 0.0625 mM
3-chloro-1-(4-hydroxyphenyl)propan-1-one
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irreversible and potent inhibitor, about 30% residual activity at 0.06 mM, 2-oxoglutarate prevents the enzyme from inactivation
4-amino-2-fluorobutanoate
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reversible, competitive to 4-aminobutanoate
4-Amino-hex-5-enoic acid
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substrate analogue, irreversible, in vitro and in vivo
4-Aminohex-5-ynoic acid
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irreversible, in vitro and in vivo, kinetics
6-Azauracil
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63% inhibition at 1 mM, reversible by dialysis, not by pyridoxal phosphate addition
Ba2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
Baclofen
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injection of 0.01 mg/g body weight reduces GABA-T mRNA level 2fold; i.p. injection of sexually regressed female goldfish results in significant increase in serum luteinising hormone after 6 h. About 2fold decrease both in glutamic acid decarboxylase 67 and gamma-aminobutanoate transaminase mRNa in the hypothalamus
beta-cypermethrin
GABA transaminase activity detected is significantly decreased in the cerebral cortex of mice 2 h after beta-cypermethrin administration. beta-Cypermethrin (80 mg/kg) significantly increases GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. The number of positive granules is increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg beta-cypermethrin. No significant changes are found in glutamate decarboxylase activity, or the expression of GABA transaminase protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg beta-cypermethrin causes a significant decrease in GABAA receptors mRNA expression 4 h after administration
Ca2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
Cd2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
cis-3-aminocyclohex-4-ene-1-carboxylic acid
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conformationally rigid analogue of vigabatrin, mechanism
Co2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
Divalent metal ions
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with decreasing efficiency: Hg2+, Cd2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
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DL-3-amino-1-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
DL-trans-4-amino-2-cyclopentene-1-carboxylic acid
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analogue of 4-aminobutanoate, vigabatrin
ethanolamine O-sulfate
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active-site directed, ir, in vitro and in vivo, kinetics
falcarindiol
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active-site directed, irreversible, 23% residual activity at 14 mM, isolate of root of Angelica dahurica
glycine
competitive inhibitor of pyruvate-dependent GABA-T activity
imperatorin
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active-site directed, irreversible, 14% residual activity at 14 mM, isolate of root of Angelica dahurica
Mg2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
Mn2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
N-(4-bromophenyl)-3-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydroindeno[1,2-c]pyrazole-2(3H)-carboxamide
molecular docking to propose the binding interaction with a three-dimensional structural model of the gamma-aminobutyric acid amino transferase. The compound successfully binds to the active pocket of the enzyme with good predicted affinities
N-(4-bromophenyl)-3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydroindeno[1,2-c]pyrazole-2(3H)-carboxamide
molecular docking to propose the binding interaction with a three-dimensional structural model of the gamma-aminobutyric acid amino transferase. The compound successfully binds to the active pocket of the enzyme with good predicted affinities
Ni2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
propan-2-one N-(2,4-dimethylphenyl)semicarbazone
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44% inhibition at 0.25 mM
S-vigabatrin
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ratio kinact/KI is1.7 per min and mM at pH 8.5, 0.11per min and mM at pH 6.5, respectively
Sr2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
(1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid
i.e. CPP-115, high inhibition of GABA-AT. Potential mechanism of inactivation of GABA-AT by CPP-115, overview. CPP-115 has been designed to inactivate GABA-AT via a Michael addition mechanism that would lead to a covalent adduct with the enzyme, similar to that with vigabatrin. But it is discovered from the crystal structure of GABAT inactivated by CPP-115 that the enzyme forms a noncovalent, tightly bound complex with CPP-115 via strong electrostatic interactions between the two carboxylate groups in the resulting metabolite with Arg192 and Arg445 in the active site. Inactivation is initiated by Schiff base formation between CPP-115 and the lysine-bound PLP, followed by gamma-proton removal and tautomerization, resulting in a highly reactive Michael acceptor. Before Lys329 can attack this Michael acceptor, catalytic hydrolysis of the difluoromethylenyl group occurs, leading to the PLP-bound dicarboxylate metabolite, which elicits a conformational change in the enzyme and tightly binds to Arg192 and Arg445 via electrostatic interactions. Molecular dynamic simulations and computer modeling indicate a movement of the difluoromethylenyl group of the Michael acceptor away from Lys329 upon enzyme-catalyzed tautomerization, leaving it too far away from Lys329 for nucleophilic attack. The enzyme catalyzes its hydrolysis instead
(1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid
i.e. CPP-115, high inhibition of GABA-AT. Potential mechanism of inactivation of GABA-AT by CPP-115, overview. CPP-115 has been designed to inactivate GABA-AT via a Michael addition mechanism that would lead to a covalent adduct with the enzyme, similar to that with vigabatrin. But it is discovered from the crystal structure of GABAAT inactivated by CPP-115 that the enzyme forms a noncovalent, tightly bound complex with CPP-115 via strong electrostatic interactions between the two carboxylate groups in the resulting metabolite with Arg192 and Arg445 in the active site. Inactivation is initiated by Schiff base formation between CPP-115 and the lysine-bound PLP, followed by gamma-proton removal and tautomerization, resulting in a highly reactive Michael acceptor. Before Lys329 can attack this Michael acceptor, catalytic hydrolysis of the difluoromethylenyl group occurs, leading to the PLP-bound dicarboxylate metabolite, which elicits a conformational change in the enzyme and tightly binds to Arg192 and Arg445 via electrostatic interactions. Molecular dynamic simulations and computer modeling indicate a movement of the difluoromethylenyl group of the Michael acceptor away from Lys329 upon enzyme-catalyzed tautomerization, leaving it too far away from Lys329 for nucleophilic attack. The enzyme catalyzes its hydrolysis instead
(S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid
i.e. OV329, synthesis method, overview
(S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid
a highly potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of addiction, design, synthesis method and mechanism, overview. Enzyme-bound structure analysis shows binding between the enzyme and a stable PLP-inhibitor noncovalent complex, rather than covalent modification, tautomeric forms of the structure of inhibitor-inactivated GABA-AT (eight theoretical tautomers of inhibitor-inactivated GABA-AT)
(S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid
a highly potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of addiction, design, synthesis method and mechanism, overview. Enzyme-bound structure analysis shows binding between the enzyme and a stable PLP-inhibitor noncovalent complex, rather than covalent modification, tautomeric forms of the structure of inhibitor-inactivated GABA-AT (eight theoretical tautomers of inhibitor-inactivated GABA-AT)
4-aminohex-5-enoic acid
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i.e. gamma-vinyl GABA, competitive, does not affect transamination process of 2-oxoglutarate
beta-Alanine
competitive inhibitor of pyruvate-dependent GABA-T activity
Cu2+
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order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+
ethanol
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in presence of disulfiram, i.e. N,N,N,N-tetraethylthiuram disulfide
gabaculine
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i.e. 5-amino-1,3-cyclohexadienylcarboxylate, ir, kinetics; not its tert-butylcarbamate derivative
Muscimol
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injection of 0.001 mg/g body weight reduces GABA-T mRNA level 15fold; i.p. injection of sexually regressed female goldfish results in significant increase in serum luteinising hormone after 6 h. About 10fold decrease in glutamic acid decarboxylase 65 and 15fold in gamma-aminobutanoate transaminase mRNa in the hypothalamus
ornithine
competitive inhibitor of pyruvate-dependent GABA-T activity
vigabatrin
competitive inhibitor of pyruvate-dependent GABA-T activity
vigabatrin
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triggers a massive synaptic plasticity in retinal areas showing a normal layering of the retina shown by the withdrawal of rod but not cone photoreceptor terminals from the outer plexiform layers towards their cell bodies. Both rod bipolar cells and horizontal cells exhibit dendritic sprouting into the photoreceptor nuclear layer. Withdrawing rod photoreceptors appear to form ectopic contacts with growing postsynaptic dendrites. Neuronal plasticity is highly suggestive of an impaired glutamate release by photoreceptors
vigabatrin
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gamma-vinyl GABA, anticonvulsant, induces spontaneous release of 4-aminobutanoate
vigabatrin
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chronical administration via drinking water at 30 and 81 mg per kg and day. Vigabatrin completely and reversibly eliminates the psychophysical evidence of tinnitus at both doses
vigabatrin
FDA-approved drug, inactivator of GABA-AT, moderate activity
additional information
a series of gamma-aminobutyric acid (GABA) derivatives obtained from 4-(1,3-dioxoisoindolin-2-yl)butanoic acid are synthesized and analyzed as inhibitory ligands docking against human ABAT as well as pig ABAT receptors. Active site docking study, overview
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additional information
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no inhibition by 6-azauridine, 6-azauridine 5'-phosphate, uracil, (iso)orotic acid, cytosine, thymine, dihydrothymine, 2-thiocytosine, thiourea; not inhibitory: 5-aminouracil
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additional information
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no inhibition by chelating agents, non-substrate L- or D-amino acids, metal ions
-
additional information
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the methanol extract from Melissa officinalis is a potent in vitro inhibitor of GABA-T with IC50 of 0.55 mg/ml, inhibition decreases in the order: methanol extract, water extract, ethyl acetate extract and hexane extract (not inhibitory)
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additional information
molecular dynamics simulations, design of mechanism-based inhibitors, drug design, overview
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additional information
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no inhibition by 3-aminopropane-1-sulfonic acid, isoguvacine (i.e. 1,2,3,4-tetrahydro-1-methyl-3-pyridine carboxylic acid), baclofen (i.e. beta-(aminomethyl)-4-chlorobenzenepropanoic acid), bicuculline, picrotoxin, Schistocerca gregaria: antiserum against sheep enzyme
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additional information
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no inhibition by chelating agents, non-substrate L- or D-amino acids, metal ions
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additional information
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(+/-)-(1S,3S,4S)-3-amino-4-fluorocyclohexanecarboxylic acid and (cis)-3-amino-5,5-difluorocylcohexanecarboxylic acid are no an inhibitors of GABA-AT at a concentration of 10 mM
-
additional information
a series of gamma-aminobutyric acid (GABA) derivatives obtained from 4-(1,3-dioxoisoindolin-2-yl)butanoic acid are synthesized and analyzed as inhibitory ligands docking against human ABAT as well as pig ABAT receptors. Active site docking study, overview
-
additional information
molecular dynamics simulations, design of mechanism-based inhibitors, drug design, overview
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