Insights Into Mutations Induced Conformational Changes and Rearrangement of Fe²⁺ Ion in pncA Gene of Mycobacterium tuberculosis to Decipher the Mechanism of Resistance to Pyrazinamide.

ABSTRACT: Pyrazinamide (PZA) is the first-line drug commonly used in treating Mycobacterium tuberculosis (Mtb) infections and reduces treatment time by 33%. This prodrug is activated and converted to an active form, Pyrazinoic acid (POA), by Pyrazinamidase (PZase) enzyme. Mtb resistance to PZA is the outcome of mutations frequently reported in pncA, rpsA, and panD genes. Among the mentioned genes, pncA mutations contribute to 72-99% of the total resistance to PZA. Thus, considering the vital importance of this gene in PZA resistance, its frequent mutations (D49N, Y64S, W68G, and F94A) were investigated through in-depth computational techniques to put conclusions that might be useful for new scaffolds design or structure optimization to improve the efficacy o

SUBMITTER: Nangraj AS 

PROVIDER: S-EPMC8174790 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature