Structural mechanism for rifampicin inhibition of bacterial rna polymerase.

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Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA

Structural mechanism for rifampicin inhibition of bacterial rna polymerase.

Cell. 2001 Mar 23;104(6):901-12.

PubMed ID

11290327 [ View in PubMed

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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 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rifampicin	DNA-directed RNA polymerase subunit beta	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details