title: On the mechanism of rifampicin inhibition of RNA synthesis.
abstract: The mechanism of rifampicin inhibition of Escherichia coli RNA polymerase was studied with a newly developed steady state assay for RNA chain initiation and by analysis of the products formed with several 5'-terminal nucleotides. The major effect of rifampicin was found to be a total block of the translocation step that would ordinarily follow formation of the first phosphodiester bond. These effects were incorporated into a steric model for rifampicin inhibition. Additional minor effects of the enzyme bound inhibitor were to increase slightly the lifetime of RNA polymerase on the lambdaPR' promoter and to increase by two the apparent Michaelis constants of the initiating triphosphates. The products formed by RNA polymerase in the presence of rifampicin belong nearly exclusively to the class pppPupN. No evidence for the accumulation of such molecules was obtained in vivo.
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007700:Kinetics; D012329:RNA, Bacterial / Q000096:biosynthesis*; D012293:Rifampin / Q000494:pharmacology*; D013696:Temperature; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D012329:RNA, Bacterial; D006160:Guanosine Triphosphate; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin