摘要
碳青霉烯类β-内酰胺抗生素包括亚胺培南和美罗培南等,优点是耐丝氨酸β-内酰胺酶,但是近年来发现金属β-内酰胺酶可以使其水解导致耐药性。以VIM型金属β-内酰胺酶为例,用生物信息学方法,通过对14种VIM型氨基酸序列比对以及结合动力学参数系统分析其结构和功能的关系,确定了结合Zn(Ⅱ)发挥催化作用的保守残基,还发现L3环区也影响碳青霉烯类的水解。针对碳青霉烯类抗生素耐药性解析金属β-内酰胺酶催化的关键残基,可为合理设计其抑制剂奠定基础。
Carbapenem β-lactam antibiotics,such as imipenem and meropenem,are generally resistant to serine β-lactamases.However,it was found recently that metallo β-lactamases effectively catalyze the hydrolysis of such antibiotics,which is the major cause of the resistance of bacteria to carbapenems.Since the primary sequences of VIM metallo β-lactamases are now available,along with structure and kinetic data for some of them,their essential residues for catalyzed hydrolysis of carbapenems was studied using bioinformatics methods.Through sequence alignment and analysis of the structure-function relationship,conserved(ligand) residues binding to Zn(Ⅱ) as active sites and the effects of L3 loop on the hydrolysis of carbapenems were identified.The results will be useful for rational design of metallo β-lactamase inhibitors due to the resistance to carbapenems.The study of the active site and mechanism of action of VIM metallo β-lactamases could lead to a rational design of inhibitors to be co-administrated with carbapenems.
出处
《大连工业大学学报》
CAS
北大核心
2012年第3期172-176,共5页
Journal of Dalian Polytechnic University