新德里金属β-内酰胺酶-1及其突变体结构与功能研究进展  

The structures and functions of New Delhi metallo β-lactamase-1 and its mutants:an updates

作　　者：高翔[1] 高越 祝成亮[1] 胡振夏 沈秉正[1] GAO Xiang;GAO Yue;ZHU Chengliang;HU Zhenxia;SHEN Bingzheng(Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院,湖北武汉430060

出　　处：《生物资源》2020年第2期173-180,共8页Biotic Resources

基　　金：国家自然科学基金项目(31700086)。

摘　　要：耐药菌株所分泌表达的新德里金属β-内酰胺酶-1(New Delhi Metalloβ-lactamase-1,NDM-1)是金属-β-内酰胺酶家族的成员,能够催化几乎所有β-内酰胺类抗生素的水解,其迅速传播已成为人类健康的严重威胁。我国是产该酶病原菌分离率较高的国家之一,绝大部分为革兰氏阴性菌。到目前为止,全世界已报道了由16个突变位点和1个插入位点所形成的21种不同的NDM突变体,这些突变体的核酸序列通过单个或多个碱基取代或插入而改变。本文总结了NDM-1的结构及催化水解机理,对其结构中α-螺旋、β-折叠和环区结构进行了探讨,并基于此突变位点对该酶结构的影响进行了分析。这些区域所发生的突变,直接影响其水解底物的活性。深入了解这些突变对其结构和功能方面的影响,对于在分子水平上的进化研究具有十分重要的意义。New Delhi Metallo β-lactamase-1(NDM-1)secreted by drug-resistant strains is a member of the metal-β-lactamase family,which is capable of catalyzing almost all β-lactams. The rapid spread of NDM-1 has become a serious threat to human health. China is one of the countries with high isolation rate of the pathogens producing this enzyme,and most of them are Gram-negative bacteria. To date,21 different NDM mutants have been reported. These mutants are formed by sixteen mutation sites and one insertion site,and the nucleic acid sequences of these mutants are altered by single or multiple base substitutions or insertions. This paper summarizes the structure and catalytic hydrolysis mechanism of NDM-1 and discusses the structure of α-helix,β-sheet and loop region. Based on the structural analysis of the effect of the mutation site,the mutations in these regions directly affect the activity of the hydrolyzed substrate. An in-depth understanding of the effects of these mutations on their structure and function is of great importance for evolutionary studies at the molecular level.

关 键 词：新德里金属β⁃内酰胺酶⁃1 突变体 结构与功能 

分 类 号：Q936[生物学—微生物学]