DNA-dependent RNA polymerase (Mycobacterium tuberculosis) (RNAP (Mtb))

DNA-dependent RNA polymerase from Mycobacterium tuberculosis is a large, multi-subunit enzyme complex essential for bacterial viability and gene expression by catalyzing the transcription of DNA into RNA. It consists of the core enzyme (α2ββ’ω) and a variable sigma subunit that confers promoter specificity and regulates transcription initiation. Mtb RNAP is fundamentally different from human RNA polymerases in its structure and mechanism, which forms the basis for selective inhibition by drugs such as rifampicin. Rifampicin binds the β subunit of the enzyme, blocking the initiation of RNA synthesis, and resistance commonly results from mutations in the rpoB gene coding for this subunit. The enzyme's regulation involves numerous transcription factors, including RbpA, which stabilizes sigma factor binding and is crucial for adaptation to environmental stress. This target's essentiality and mechanistic uniqueness make it one of the most important drug targets for tuberculosis therapy, both for current front-line drugs and as a focus for new antibiotic development.

Other names

Mtb RNA polymeraseMycobacterium tuberculosis RNA polymeraseMtb RNAPDNA-directed RNA polymerase (Mycobacterium tuberculosis)

Inhibition of RNA synthesis (e.g., rifampicin binds the β subunit and blocks transcription initiation); Competitive inhibition at nucleotide-binding sites (for nucleotide analogs)