Structural mechanism for rifampicin inhibition of bacterial rna polymerase

Cell. 2001 Mar 23;104(6):901-12. doi: 10.1016/s0092-8674(01)00286-0.


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 beta subunit deep within the DNA/RNA channel, but more than 12 A 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / genetics
  • Escherichia coli / enzymology
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / enzymology
  • Protein Conformation
  • Protein Subunits
  • Rifampin / chemistry*
  • Rifampin / pharmacology*
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Thermus / enzymology*


  • Protein Subunits
  • DNA-Directed RNA Polymerases
  • Rifampin

Associated data

  • PDB/1I6V