Abstract
Gama aminobutyrate aminotransferase (GABA-AT) (500aa) is a pyridoxal phosphate dependent GABA degrading homodimeric enzyme of 50-kD subunits, a potential drug target to control epilepsy. There are no records of the structural characterization of GABA-AT. So, in this experiment attempt has been made to predict homology model of the human GABA-AT on the template of the pig liver GABA-AT sequence. Structural characterization of GABA-AT would greatly advance the development of novel lead compounds targeting this molecule. Homology modeling was carried out using MODELLER 9.12, SWISS model and Phyre2 Servers. Analysis suggested that the SWISS model had better scores in ERRAT and RAMPAGE compared to MODELLER and Phyre2 models. Though, MODELLER scored highest in PROCHECK analysis. After refinement, MODELLER and SWISS models scored better than Phyre2 models. Analysis of active sites suggested that SWISS model had largest numbers of cavities and pockets compared to MODELLER and SWISS models. 3D structure of SWISS model had 119 numbers of cavities while Phyre2 had 65 cavities and MODELLER model had 62 cavities. It could be assumed from the evaluation results that the refined model of SWISS model had an edge over the other two structures. From this study we could suggest that the homology models of GABA-AT generated by MODELLER and SWISS model both were reliable could be used for further studies.
