Examining the role of protein structural dynamics in drug resistance in Mycobacterium tuberculosis.

ABSTRACT: Antimicrobial resistance represents a growing global health problem. The emergence of novel resistance mechanisms necessitates the development of alternative approaches to investigate the molecular fundamentals of resistance, leading ultimately to new strategies for counteracting them. To gain deeper insight into antibiotic-target interactions, the binding of the frontline anti-tuberculosis drug isoniazid (INH) to a target enzyme, InhA, from Mycobacterium tuberculosis was studied using ultrafast two-dimensional infrared (2D-IR) spectroscopy and molecular simulations. Comparing wild-type InhA with a series of single point mutations, it was found that binding of the INH-NAD inhibitor to susceptible forms of the enzyme increased the vibrational coupling between residues located in the

SUBMITTER: Shaw DJ 

PROVIDER: S-EPMC5863454 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature