New inhibitors targeting bacterial RNA polymerase.
- Author:
Jing SHI
1
;
Yu FENG
1
Author Information
1. Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China.
- Publication Type:Journal Article
- MeSH:
Antitubercular Agents;
therapeutic use;
Bacteria;
drug effects;
enzymology;
DNA-Directed RNA Polymerases;
metabolism;
Drug Discovery;
trends;
Drug Resistance, Bacterial;
Enzyme Activation;
drug effects;
Enzyme Inhibitors;
pharmacology;
Humans;
RNA, Bacterial;
Tuberculosis;
drug therapy;
enzymology
- From:
Journal of Zhejiang University. Medical sciences
2019;48(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.
