Mycobacterium tuberculosis DNA-directed RNA polymerase subunit beta (RpoB) (RpoB)

The Mycobacterium tuberculosis DNA-directed RNA polymerase subunit beta, encoded by the rpoB gene, is a vital enzyme component that catalyzes the polymerization of ribonucleotides into RNA using a DNA template (UniProt: P9WGY9). It forms the catalytic core of the RNA polymerase complex, which is essential for the survival, growth, and pathogenesis of the bacterium (PubMed: 29025990). This subunit is the primary target for rifamycins, such as rifampicin, which are cornerstone antibiotics in the treatment of tuberculosis (StatPearls: Rifampin). Rifampicin binds to the beta subunit near the RNA/DNA channel, sterically hindering the elongation of the nascent RNA chain after the first few nucleotides are added (PubMed: 11586040). Mutations within a specific 81-base pair region of the rpoB gene, known as the rifampicin resistance-determining region (RRDR), are responsible for approximately 95% of rifampicin resistance in clinical isolates (PubMed: 24814667). Consequently, RpoB is not only a critical therapeutic target but also a major diagnostic biomarker for identifying multidrug-resistant tuberculosis (MDR-TB). The structural conservation of this subunit across bacteria makes it a focal point for broad-spectrum antibiotic research, though specificity for the M. tuberculosis variant is crucial for minimizing off-target effects on human mitochondrial RNA polymerase. Therapeutic challenges include the rapid emergence of resistant strains and the potent induction of human metabolic enzymes by rifamycin ligands, leading to significant drug-drug interactions.

Other names

RNA polymerase beta subunitRpoBDNA-directed RNA polymerase subunit betarpoBMycobacterium tuberculosis RpoB

Inhibition of bacterial RNA synthesis by binding to the beta subunit of DNA-directed RNA polymerase, which sterically blocks the elongation of the nascent RNA chain (PubMed: 11586040).