期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.690902
关键词
ClpP; protease; acyldepsipeptide; antibiotic; mode of action; conformational control; drug discovery
资金
- Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) within the TRR 261 [398967434]
- Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) within the Cluster of Excellence Controlling Microbes to Fight Infection EXC 2124 [390838134]
- State Ministry of Science, Research and Arts, Baden-Wurttemberg
- Open Access Publishing Fund of University of Tubingen
The article summarizes the discovery and evaluation of the caseinolytic protease Clp as a novel antibiotic target, as well as the molecular mechanisms and physiological effects of the interaction between ADEP and ClpP.
Rising antibiotic resistance urgently calls for the discovery and evaluation of novel antibiotic classes and unique antibiotic targets. The caseinolytic protease Clp emerged as an unprecedented target for antibiotic therapy 15 years ago when it was observed that natural product-derived acyldepsipeptide antibiotics (ADEP) dysregulated its proteolytic core ClpP towards destructive proteolysis in bacterial cells. A substantial database has accumulated since on the interaction of ADEP with ClpP, which is comprehensively compiled in this review. On the molecular level, we describe the conformational control that ADEP exerts over ClpP, the nature of the protein substrates degraded, and the emerging structure-activity-relationship of the ADEP compound class. On the physiological level, we review the multi-faceted antibacterial mechanism, species-dependent killing modes, the activity against carcinogenic cells, and the therapeutic potential of the compound class.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据