Homology modeling of γ-aminobutyrateaminotransferase, a pyridoxal phosphate-dependent enzyme of Homo sapiens: Molecular modeling approach to rational drug design against epilepsy

Abstract

γ-Aminobutyrate aminotransferase (GABA-AT) is a pyridoxal phosphate dependent homodimeric enzyme of 50-kD subunits. It is a potential drug target against epilepsy. The three-dimensional structure of GABA-AT is not experimentally known, and we thus resorted to homology modelling to build a model based on x-ray crystal structure of pig liver GABA-AT to 3.0 Å resolution. Knowledge of the threedimensional structure of GABA-AT would greatly advance the development of novel lead compounds targeting this molecule. The protein’s conservity was verified by performing multiple alignments using ClustalW and MUSCLE programs. The model was further checked for its correctness by predicting the 2D and 3D structures, which validates the structure.

Key words: γ-Aminobutyrate aminotransferase (GABA-AT), epilepsy, crystal structure, homology modeling, BLAST, template.