Rifampicin inhibits transcription by targeting which subunit?
Rifampicin, an ansamycin antibiotic used against tuberculosis, binds within a deep pocket of the RNA polymerase beta subunit encoded by rpoB gene, lined by residues of rifampicin resistance determining region. Located about twelve angstroms from active site magnesium, it does not block NTP binding but physically obstructs path of growing RNA chain longer than two to three nucleotides, acting as steric block. Binding creates highly stable drug-enzyme complex with nanomolar affinity. Eukaryotic polymerases II, I, III lack this pocket and remain insensitive. Mutations in RRDR cause clinical resis
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 9: Rifampicin targets beta subunit; Nature Struct Biol, Rifampicin inhibition mechanism