Modeling and Docking Study of GABA-AT Protein in Mycobacterium Tuberculosis-A Computational Approach

Abstract

Tuberculosis, a transmittable killer disease caused by Mycobacterium tuberculosis whose pathogenesis is poorly understood. The treatment available for the anti-mycobacterial activity has poor observance because of the uprising of the drug resistance strains resulted by the prolonged treatment giving the chance to the microbe to develop resistance. Hence, there is an urgent need to identify novel compounds from marine sources which are having antimicrobial activity. GABA-AT is an important enzyme involved in GABA shunt pathway of TCA cycle which has a role in virulence of Mycobacterium tuberculosis as it is a PLP dependent enzyme. In this present study, the 3D structure of GABA-AT was generated by using SWISSMODEL and validated using various methods. The model generated was validated and secondary structural analysis was predicted using YASPIN. Thereafter, the active site was predicted and further used the residues for docking. The acquired model was docked with the known inhibitors of GABA-AT and marine compounds having anti-tuberculosis activity. The comparative analysis of protein ligand interaction between known inhibitor and marine compounds were studied. Among them, Heteronemin has the best binding energy (-9.19Kcal/mol) which indicates that the marine compound can be used for inhibiting the activity of GABA-AT in Mycobacterium tuberculosis and can be proposed as valuable drug candidate.