Structural Basis for Carbapenem-Hydrolyzing Mechanisms of Carbapenemases Conferring Antibiotic Resistance

International Journal of Molecular Sciences

Jeong Ho Jeon¹  Jung Hun Lee¹  Jae Jin Lee²  Kwang Seung Park²  Asad Mustafa Karim²  Chang-Ro Lee²  Byeong Chul Jeong²  Sang Hee Lee¹ 

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

关键词: carbapenemases;    carbapenems;    structure;    catalytic mechanism;   

DOI  :  10.3390/ijms16059654

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.