Is it easy to stop RNA polymerase?
Among transcription factors that bind to bacterial RNA polymerase (RNAP) and modulate its activity, a number of small molecules irreversibly inhibit RNAP thereby causing cell death. To be of clinical significance such inhibitors must (1) inhibit a broad range of bacterial RNAPs but not affect human cells, (2) penetrate bacterial cell walls and (3) circumvent bacterial resistance mechanisms. Rifamycins, the only class of RNAP inhibitors that have found their way into clinical practice, are widely used in the treatment of tuberculosis and leprosy. However, the practical value of this class of antibiotics is limited by a rapid rise in resistant bacterial isolates. In this review we focus on recent advances in studies of prokaryotic transcription that allow a detailed structural and functional characterization of a number of RNAP/rifamycins complexes, thereby opening new opportunities for the design of superior antibacterial agents.
Artsimovitch
Irina
I
Department of Microbiology, The Ohio State University, Columbus, Ohio, USA.
Vassylyev
Dmitry G
DG
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D012294:Rifamycins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000900:Anti-Bacterial Agents; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases