Characterization of a catalase-peroxidase variant (L333V-KatG) identified in an INH-resistant Mycobacterium tuberculosis clinical isolate.

ABSTRACT: Mycobacterium tuberculosis catalase-peroxidase (Mt-KatG) is a bifunctional heme-dependent enzyme that has been shown to activate isoniazid (INH), the widely used antibiotic against tuberculosis (TB). The L333V-KatG variant has been associated with INH resistance in clinical M. tuberculosis isolates from Mexico. To understand better the mechanisms of INH activation, its catalytic properties (catalase, peroxidase, and IN-NAD formation) and crystal structure were compared with those of the wild-type enzyme (WT-KatG). The rate of IN-NAD formation mediated by WT-KatG was 23% greater than L333V-KatG when INH concentration is varied. In contrast to WT-KatG, the crystal structure of the L333V-KatG variant has a perhydroxy modification of the indole nitrogen of W107 from MYW ad

SUBMITTER: Uribe-Vazquez B 

PROVIDER: S-EPMC10839757 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature