The Structural Basis of Mycobacterium tuberculosis RpoB Drug-Resistant Clinical Mutations on Rifampicin Drug Binding.

ABSTRACT: Tuberculosis (TB), caused by the Mycobacterium tuberculosis infection, continues to be a leading cause of morbidity and mortality in developing countries. Resistance to the first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF), is a major drawback to effective TB treatment. Genetic mutations in the β-subunit of the DNA-directed RNA polymerase (rpoB) are reported to be a major reason of RIF resistance. However, the structural basis and mechanisms of these resistant mutations are insufficiently understood. In the present study, thirty drug-resistant mutants of rpoB were initially modeled and screened against RIF via a comparative molecular docking analysis with the wild-type (WT) model. These analyses prioritized six mutants (Asp441Val, Ser456Trp, Ser456Gln, Arg

SUBMITTER: Amusengeri A 

PROVIDER: S-EPMC8839920 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature