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赋予抗生素抗性的碳青霉烯酶水解碳青霉烯机制的结构基础。

Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance.

作者信息

Jeon Jeong Ho, Lee Jung Hun, Lee Jae Jin, Park Kwang Seung, Karim Asad Mustafa, Lee Chang-Ro, Jeong Byeong Chul, Lee Sang Hee

机构信息

National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 449-728, Korea.

出版信息

Int J Mol Sci. 2015 Apr 29;16(5):9654-92. doi: 10.3390/ijms16059654.

DOI:10.3390/ijms16059654
PMID:25938965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4463611/
Abstract

Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity.

摘要

碳青霉烯类抗生素（亚胺培南、美罗培南、比阿培南、厄他培南和多立培南）是β-内酰胺类抗菌药物。由于碳青霉烯类抗生素在所有β-内酰胺类药物中具有最广的抗菌谱，主要用于治疗多重耐药革兰氏阴性菌感染，因此碳青霉烯酶的出现和传播成为一个重大的公共卫生问题。碳青霉烯酶是最具多样性的β-内酰胺酶家族，能够水解碳青霉烯类抗生素和许多其他β-内酰胺类药物。根据二价阳离子对酶激活的依赖性，碳青霉烯酶可分为金属碳青霉烯酶（锌依赖性B类）和非金属碳青霉烯酶（锌非依赖性A、C和D类）。许多研究提供了各种碳青霉烯酶的结构。在此，我们对碳青霉烯酶-碳青霉烯复合物以及碳青霉烯酶的三维结构进行全面而系统的综述。我们更新了关于各类碳青霉烯酶酶促机制的最新研究，并总结了关于获得碳青霉烯酶活性至关重要的区域和残基的结构见解。

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