STRUCTURAL VARIATION AND TRANSITIONAL ANALYSIS OF EMBB RECEPTOR WITH ITS MUTANTS LEADING TO DRUG RESISTANCE IN TUBERCULOSISVAMIKA KARN, VARUN P. TALATI, SHASHANK S. KAMBLE AND VIRUPAKSHA A. BASTIKAR
Ethambutol is an essential anti-tuberculosis drug widely used for the treatment of multidrug resistant tuberculosis (MDR-TB). However, resistance to ethambutol has been observed mainly due to mutations in probable arabinosyltransferase B (embB). In the current paper, we study the conformational changes occurring in probable arabinosyltransferase B due to mutations and their effect on the drug interactions. The mutants were modeled, energy minimized and docking was performed with ethambutol to study the interaction. On comparison with the wildtype, the rmsd of mutants were in the range of 0.5- 0.65 and the average distance was 0.688. Amino acids Met306, Glu327 and Asp328 were observed to be involved in the ethambutol interaction network with the mutants having a disrupted network with these amino acids. High degree of mutations were observed between 306 and 497 amino acid positions with mutation at 306 being associated with high levels of ethambutol and multidrug resistance.