Theoretical studies on the inactivation mechanism of γ-aminobutyric acid aminotransferase.

Abstract

The inactivation mechanism of γ-aminobutyric acid aminotransferase (GABA-AT) in the presence of γ-vinyl-aminobutyric acid, an anti-epilepsy drug, has been studied by means of theoretical calculations. Density functional theory methods have been applied to compare the three experimentally proposed inactivation mechanisms (Silverman et al., J. Biol. Chem., 2004, 279, 363). All the calculations were performed at the B3LYP/6-31+G(d,p) level of theory. Single point solvent calculations were carried out in water, by means of an integral equation formalism-polarizable continuum model (IEFPCM) at the B3LYP/6-31+G(d,p) level of theory. The present calculations provide an insight into the mechanistic preferences of the inactivation reaction of GABA-AT. The results also allow us to elucidate the key factors behind the mechanistic preferences. The computations also confirm the importance of explicit water molecules around the reacting center in the proton transfer steps.

• Authors: A T Durak, H Gökcan, F A S Konuklar
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 9 Issue 14 Pg. 5162-71 (Jul 21 2011) ISSN: 1477-0539 [Electronic] England
• PMID: 21647516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• gamma-Aminobutyric Acid
• 4-Aminobutyrate Transaminase

Topics

• 4-Aminobutyrate Transaminase (chemistry, metabolism)
• Molecular Structure
• Quantum Theory
• Stereoisomerism
• gamma-Aminobutyric Acid (chemistry)