Molecular principles behind pyrazinamide resistance due to mutations in panD gene in Mycobacterium tuberculosis

Gene
Bharati PandeyAbhinav Grover

Abstract

The latest resurrection of drug resistance poses serious threat to the treatment and control of the disease. Mutations have been detected in panD gene in the Mycobacterium tuberculosis (Mtb) strains. Mutation of histidine to arginine at residue 21 (H21R) and isoleucine to valine at residue 29 (I49V) in the non-active site of panD gene has led to PZA resistance. This study will help in reconnoitering the mechanism of pyrazinamide (PZA) resistance caused due to double mutation identified in the panD gene of M. tuberculosis clinical isolates. It is known that panD gene encodes aspartate decarboxylase essential for β-alanine synthesis that makes it a potential therapeutic drug target for tuberculosis treatment. The knowledge about the molecular mechanism conferring drug resistance in M. tuberculosis is scarce, which is a significant challenge in designing successful therapeutic drug. In this study, structural and dynamic repercussions of H21R-I49V double mutation in panD complexed with PZA have been corroborated through docking and molecular dynamics based simulation. The double mutant (DM) shows low docking score and thus, low binding affinity for PZA as compared to the native protein. It was observed that the mutant protein exhib...Continue Reading

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Citations

Feb 6, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ondrej JandourekMartin Dolezal
Nov 25, 2016·Journal of Cellular Biochemistry·Salma JamalAbhinav Grover
Mar 2, 2017·Journal of Cellular Biochemistry·Bharati PandeyAbhinav Grover
Nov 17, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pavel MucajiJosef Jampilek
Oct 6, 2017·Journal of Cellular Biochemistry·Mansi AggarwalAbhinav Grover
Jan 18, 2018·Chemical Biology & Drug Design·Sharad VermaAbhinav Grover
Jul 14, 2018·Journal of Cellular Biochemistry·Bharati PandeyPradeep Sharma
Sep 14, 2019·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Majid Faridgohar
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May 15, 2018·Frontiers in Cellular and Infection Microbiology·H M Adnan HameedTianyu Zhang
Sep 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan ZitkoMartin Doležal

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