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新德里金属β-内酰胺酶-1 变体的结构和功能见解。

Structural and functional insight of New Delhi Metallo β-lactamase-1 variants.

机构信息

Medical Microbiology & Molecular Biology Lab, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202 002, UP, India.

出版信息

Future Med Chem. 2018 Jan;10(2):221-229. doi: 10.4155/fmc-2017-0143. Epub 2017 Dec 5.

Abstract

New Delhi Metallo β-lactamase-1 (NDM-1) is a member of the Metallo-β-lactamase family, capable of catalyzing the hydrolysis of all β-lactam antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a worldwide concern to health workers. Seventeen different variants of NDM have been reported so far, across the world. These variants varied in their sequences either by single or multiple amino acid substitutions. This review summarizes the crystal structure of NDM and provides a comparative analysis of all variants. Moreover, we have for the first time highlighted the role of α-helix, β-sheet and loop structures of NDM enzyme, having different mutations occurred in these regions. The effect of these substitutions on its structure and functional aspect has to be thoroughly understood to design effective inhibitors in future.

摘要

新德里金属β-内酰胺酶-1(NDM-1)是金属β-内酰胺酶家族的成员,能够催化所有β-内酰胺抗生素的水解。NDM 产生者(“超级细菌”)的快速传播引起了卫生工作者的全球关注。迄今为止,已经在全球范围内报告了 17 种不同的 NDM 变体。这些变体在其序列上存在单个或多个氨基酸取代的差异。本综述总结了 NDM 的晶体结构,并对所有变体进行了比较分析。此外,我们首次强调了 NDM 酶的α-螺旋、β-折叠和环结构的作用,这些区域发生了不同的突变。必须深入了解这些取代对其结构和功能方面的影响,以便在未来设计有效的抑制剂。

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