title: 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.affiliation: Istanbul Technical University Informatics Institute, Computational Science and Engineering Programme, Ayazağa Campus, 34469, Maslak, Istanbul, Turkey.
authors.forename: A T
authors.initials: AT
authors.lastname: Durak
authors.forename: H
authors.initials: H
authors.lastname: Gökcan
authors.forename: F A S
authors.initials: FA
authors.lastname: Konuklar
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D011789:Quantum Theory; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase