细菌ClpP蛋白酶功能及其抗菌药物靶点的研究进展  

Research progress on the function,drug target and its development of bacterial ClpP

作　　者：颜骊颖 张亚培[2] 董世雷[2] Yan Li-ying;Zhang Ya-pei;Dong Shi-lei(School of Medical Technology,Zhejiang Chinese Medical University,Hangzhou 310053;Department of Clinical Laboratory,Zhejiang Hospital,Hangzhou 310013)

机构地区：[1]浙江中医药大学医学技术学院,杭州310053 [2]浙江医院医学检验科,杭州310013

出　　处：《中国抗生素杂志》2022年第1期15-21,共7页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(No.81801978);浙江省医药卫生科技计划项目(No.2018KY201);浙江省公益技术研究计划项目(No.LGF21H190001)。

摘　　要：ClpP(Casein lytic proteinase P)是一种广泛存在于真核细胞和原核生物中的丝氨酸蛋白酶,可与多种类型AAA+(ATPase associated with various cellular activity)超家族ATP酶组成多种ClpP蛋白酶复合物,其主要功能是清除或降解细菌胞内合成不当、受损伤、变性聚集或无用的蛋白,并维持正常代谢和压力刺激下胞内蛋白质的动态平衡。近年研究表明,细菌ClpP可协助病原菌在宿主体内生存、繁殖和播散,ClpP在细菌致病过程中发挥重要作用,其相关致病机制也受到广泛关注。近年,细菌对抗生素耐药性不断增强,已严重威胁人类健康,ClpP蛋白酶因其独特的蛋白水解作用而成为抗菌药物研究的新靶点。本文综述了ClpP在不同病原体中的结构、分子功能和不同作用以及相应药物开发方面的研究进展。Casein lytic proteinase P(ClpP)is a serine protease that widely exists in eukaryotes and prokaryotes.It can form a variety of ClpP protease complexes with various types of AAA+(ATPase associated with various cellular activity)superfamily ATPases.Their main functions are to remove or degrade improperly synthesized,damaged,denatured or useless proteins in bacteria,and to maintain the dynamic balance of intracellular proteins under normal metabolism and adverse environmental changes.Recent studies have shown that bacterial ClpP can assist pathogens to survive,reproduce,and spread in the host.ClpP plays an important role in the pathogenic process of bacteria,and its related pathogenic mechanism has also attracted wide attention.In recent years,bacteria have become more and more resistant to antibiotics,which has been a serious threat to human health.ClpP protease has become a new target for antimicrobial research because of its unique proteolysis.This paper reviews the structure,molecular function,and different functions of ClpP in different pathogens,as well as the research progress of corresponding drug development.

关 键 词：酪蛋白水解蛋白酶P(ClpP) 蛋白降解 致病机制 酰基缩肽(ADEPs) 药物开发 

分 类 号：R978[医药卫生—药品]