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J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (1): 44-49    DOI: 10.3785/j.issn.1008-9292.2019.02.08
New inhibitors targeting bacterial RNA polymerase
SHI Jing1(),FENG Jue1,2
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Rifamycins, a group of bacterial RNA polymerase inhibitors, are the first-line antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycin-resistant bacteria, development of new RNA polymerase inhibitors that kill rifamycin-resistant 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.

Key wordsRifamycins/pharmacokinetics      Anti-bacterial agents      DNA-directed RNA polymerases/antagonists & inhibitors      Microscopy, electron      Freezing      Review     
Received: 25 July 2018      Published: 10 May 2019
CLC:  Q71  
Cite this article:

SHI Jing,FENG Jue. New inhibitors targeting bacterial RNA polymerase. J Zhejiang Univ (Med Sci), 2019, 48(1): 44-49.

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关键词: 利福霉素类/药代动力学,  抗菌药,  指导DNA的RNA聚合酶类/拮抗剂和抑制剂,  显微镜检查,电子,  冷冻,  综述 
Figure 1 Structures of inhibitors in complex with bacterial RNA polymerase
Figure 2 Chemical structures of bacterial RNA polymerase inhibitors
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