Structural mechanism for rifampicin inhibition of bacterial RNA polymerase

Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics a gainst bacterial pathogens and is a key component of anti-tuberculosis ther apy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). W e determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP beta subunit deep wi thin the DNA/RNA channel, but more than 12 Angstrom away from the active si te. The structure, combined with biochemical results, explains the effects of Rif on RNAP function and indicates that the inhibitor acts by directly b locking the path of the elongating RNA when the transcript becomes 2 to 3 n t in length.