Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Tuberculosis one of leading threat to human health worldwide. It is responsible for causing millions of deaths around the globe. WHO ranked the Pakistan 8th among 22 high burden countries of world. The resistance against pro-drug isoniazid of Mycobacterium tuberculosis has become a global threat especially in 3rd world countries. It has been considered resistance against isoniazid is directly associated with mutations in hyper variable region of KatG gene that encode the catalase-peroxidase enzyme. Mutations in KatG especially S315T and S315R are mainly responsible for resistance against Mycobacterium tuberculosis. In this study, to understand the impact of mutation, structure based systematic computational analysis was made. It has been observed that above mention mutations affect the structure of protein and its interaction with other element presents in network. Results of our studies showed that conformational changes in the structure KatG protein these changes cause the work alteration in INH binding residues at active site of KatG enzyme. We also observed the changes in interaction energy, ligand-receptor energy, electrostatic energy, salvation free energy and also ligand-receptor conformation entropy. It is assumed that respective mutations minimized the stability and flexibility of protein at INH binding residues that can cause the impaired enzyme function. We hope that this study will help to rootout the possible solution in consequences of these mutations.

Biography

Muhammad Mumtaz Khan has completed his Undergraduate degree in Microbiology from Hazara University, Manshera, Pakistan in 2005. He completed his PhD degree from University of Karachi, Karachi, Pakistan in 2014. He is currently working as Assistant Professor in Department of Microbiology University of Haripur, Haripur, Pakistan. His work in Doctoral research is on rifampicin and isoniazid associated multiple drug resistance in Mycobacterium tuberculosis in Pakistan. He has published 11 articles in international reputed journal and also made 14 NCBI/GenBank submissions.

Email: mumtaz.muhammadee@gmail.com