Mycobacterial DNA-directed RNA polymerase (RNAP)

Mycobacterial DNA-directed RNA polymerase is a multisubunit enzyme complex essential for transcription in *Mycobacterium* species, including the tuberculosis pathogen *M. tuberculosis*. This enzyme synthesizes RNA from a DNA template, thereby regulating gene expression and facilitating cellular responses to environmental changes. It consists of core subunits (typically α2ββ'ω) and is functionally assembled with sigma factors that direct promoter recognition, as well as other transcription factors that regulate activity, stress response, and complex assembly. The β subunit (encoded by rpoB) is the primary binding site for rifampicin and related antibiotics, which inhibit transcription and thus kill or inhibit bacterial growth. Resistance commonly arises through mutations in the rpoB gene. The structural and functional divergence from eukaryotic RNA polymerases permits antimicrobial selectivity but also presents a challenge in the evolution of resistance. The enzyme comprises unique taxon-specific insertions and regulatory mechanisms compared to other bacteria, which may influence drug binding and regulatory responses. Mycobacterial RNAP is a cornerstone therapeutic target for tuberculosis and multidrug-resistant tuberculosis.

Other names

DNA-dependent RNA polymeraseMycobacterial RNAPβ subunit (for major drug binding site, e.g. rpoB gene product)RNA polymerase (in the context of mycobacteria)Mtb RNAP (in *Mycobacterium tuberculosis*)

Rifampin and related drugs bind to the β subunit of RNAP, inhibiting RNA synthesis by physically blocking the elongation of the RNA chain. Experimental inhibitors (e.g., D-AAP1) bind at distinct or overlapping sites to block catalysis or stabilize non-productive conformations.