Mycobacterial RNA polymerase beta subunit (RpoB)

The mycobacterial RNA polymerase beta subunit (RpoB) is a core component of the bacterial DNA-dependent RNA polymerase holoenzyme, essential for the transcription of DNA to mRNA in *Mycobacterium tuberculosis* and related species. The enzyme complex is composed of multiple subunits (α2ββ′ω), where the β subunit forms the catalytic core responsible for RNA synthesis. RpoB serves as the direct target of rifampicin and related antibiotics—the primary drugs in tuberculosis therapy—by binding to the β subunit and inhibiting RNA polymerase activity, leading to cell death. Mutations in the rpoB gene confer resistance to rifampicin, making RpoB mutation screening a major tool in diagnosing rifampicin-resistant TB. Emerging drug discovery focuses on disrupting the interaction between RpoB and transcription factors such as CarD, which is crucial for bacterial gene expression and survival. This target is central to antitubercular therapy, but its utility is challenged by the rapid evolution of resistance.

Other names

RpoBRNA polymerase β subunitRNA polymerase beta chain

Inhibition of transcription by blocking RNA chain elongation, primarily through binding to the β subunit and preventing movement along DNA; Disruption of protein-protein interactions between RpoB and essential transcription factors such as CarD (mechanism for novel inhibitors)