Structural mechanism for rifampicin inhibition of bacterial RNA polymerase

Elizabeth A. Campbell, Nataliya Korzheva, Arkady Mustaev, Katsuhiko Murakami, Satish Nair, Alex Goldfarb, Seth A. Darst

Research output: Contribution to journalArticlepeer-review

828 Scopus citations

Abstract

Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). We determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP β subunit deep within the DNA/RNA channel, but more than 12 Å away from the active site. The structure, combined with biochemical results, explains the effects of Rif on RNAP function and indicates that the inhibitor acts by directly blocking the path of the elongating RNA when the transcript becomes 2 to 3 nt in length.

Original languageEnglish (US)
Pages (from-to)901-912
Number of pages12
JournalCell
Volume104
Issue number6
DOIs
StatePublished - Mar 23 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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