Mechanism of inactivation of gamma-aminobutyrate aminotransferase by 4-amino-5-fluoropentanoic acid. First example of an enamine mechanism for a gamma-amino acid with a partition ratio of 0.

@article{Silverman1986MechanismOI,
  title={Mechanism of inactivation of gamma-aminobutyrate aminotransferase by 4-amino-5-fluoropentanoic acid. First example of an enamine mechanism for a gamma-amino acid with a partition ratio of 0.},
  author={R. Silverman and B. Invergo},
  journal={Biochemistry},
  year={1986},
  volume={25 22},
  pages={
          6817-20
        }
}
The mechanism of inactivation of pig brain gamma-aminobutyric acid aminotransferase (GABA-T) by (S)-4-amino-5-fluoropentanoic acid (1, R = CH2CH2COOH, X = F) previously proposed [Silverman, R. B., & Levy, M. A. (1981) Biochemistry 20, 1197-1203] is revised. apo-GABA-T is reconstituted with [4-3H]pyridoxal 5'-phosphate and inactivated with 1 (R = CH2CH2COOH, X = F). Treatment of inactivated enzyme with base followed by acid denaturation leads to the complete release of radioactivity as 6-[2… Expand
Inactivation of gamma-aminobutyric acid aminotransferase by (Z)-4-amino-2-fluorobut-2-enoic acid.
TLDR
The results support an inactivation mechanism for 1 that involves normal catalytic isomerization followed by active site nucleophilic attack on the activated Michael acceptor. Expand
Mechanism-based inactivation of gamma-aminobutyric acid aminotransferase by 3-amino-4-fluorobutanoic acid.
TLDR
The mechanism of inactivation of the pyridoxal 5'-phosphate (PLP)-dependent enzyme gamma-aminobutyric acid (GABA) aminotransferase by 3-amino-4-fluorobutanoic acid has been investigated and results are not consistent with a Michael addition mechanism, but are consistent with inactivation by an enamine mechanism. Expand
Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid.
Evidence for an enamine mechanism of inactivation of pig brain gamma-aminobutyric acid (GABA) aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid is presented. apo-GABA aminotransferaseExpand
Enantiomers of 4-amino-3-fluorobutanoic acid as substrates for gamma-aminobutyric acid aminotransferase. Conformational probes for GABA binding.
TLDR
The present study suggests that the C-F bond can be utilized as a conformational probe to explore the dynamic binding process and provide insight into the bioactive conformation of substrates, which cannot be easily determined by other biophysical approaches. Expand
Action of 4-Amino-2-fluorobutanoic Acid and Other Structural Analogues on Gamma-Aminobutyric Acid Transport by Channel Catfish Brain
TLDR
Observed kinetics of inhibition of GABA transport by 4-amino-2-fluorobutanoic acid and several other structural analogues of GABA suggest that the GABA transport system in channel catfish is remarkably similar to that in mammalian brain. Expand
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TLDR
Two HPLC systems for isolating this inactivator-PLP adduct are described as well as a detailed characterization of the adduct, including the ultraviolet-visible spectrum, electrospray mass spectra, and NMR spectrum. Expand
Mechanism of inactivation and identification of sites of modification of ornithine aminotransferase by 4-aminohex-5-ynoate.
TLDR
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α-Amino acid analogues as mechanism-based inactivators of γ-aminobutyric acid aminotransferase
Abstract γ- and β-Amino acids have been used previously to inactivate γ-aminobutyric acid aminotransferase. Here it is shown that β-halo-, β-phospho-, β-sulpho- L -alanine, and vinyl- L -glycine, allExpand
3-substituted alanines inactivate γ-aminobutyric acid aminotransferase by the same mechanism as do 4-amino-5-halopentanoic acid analogues
L-Serine O-sulfate inactivates γ-aminobutyric acid aminotransferase (GABA-AT) by a mechanism that involves elimination of the leaving group and an enamine rearrangement, the same mechanism as thatExpand
Theoretical study on HF elimination and aromatization mechanisms: a case of pyridoxal 5' phosphate-dependent enzyme.
TLDR
Results allowed us to draw a conclusion for the nature of HF elimination, besides the elucidation of the mechanism preference for the inactivation mechanism, that aromatization competes with Michael addition mechanism in the presence of 5-amino-2-fluorocyclohex-3-enecarboxylic acid. Expand
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Evidence is presented to show that these compounds are mechanism-based inactivators, and experiments are described to elucidate their mechanism of action. Expand
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The pyridoxal form of alanine aminotransferase from pig heart catalyzes the a,/? elimination reaction with 3chloro-L-alanine as the substrate to form equimolar amounts of pyruvate, ammonia, andExpand
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Abstract γ-Aminobutyric acid-α-ketoglutarate transaminase from pig brain is irreversibly inactivated by 4-amino-5-halopentanoic acids. Protection from inactivation by the natural substrates, the pHExpand
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TLDR
A multistep mechanism is proposed for the reconstitution of 4-aminobutyrate aminotransferase, a dimeric protein made up of subunits of identical molecular weight that does not dissociate into subunits over a wide range of protein concentration at neutral pH. Expand
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TLDR
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