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DOI | 10.1038/s41467-018-05140-5 |
The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis | |
Feng, Han1; Liu, Xuehui1; Wang, Sheng2; Fleming, Joy3,4; Wang, Da-Cheng1; Liu, Wei5 | |
2017-12-21 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China |
英文摘要 | New Delhi metallo-beta-lactamases (NDMs), the recent additions to metallo-beta-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of beta-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 angstrom, together with NMR spectra monitoring meropenem hydrolysis. Three enzyme-intermediate/product derivatives, EI1, EI2, and EP, are trapped in these crystals. Our structural data reveal double-bond tautomerization from Delta(2) to Delta(1), absence of a bridging water molecule and an exclusive beta-diastereomeric product, all suggesting that the hydrolytic intermediates are protonated by a bulky water molecule incoming from the beta-face. These results strongly suggest a distinct mechanism of NDM-1-catalyzed carbapenem hydrolysis from that of penicillin or cephalosporin hydrolysis, which may provide a novel rationale for design of mechanism-based inhibitors. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000418567200009 |
WOS关键词 | METALLO-BETA-LACTAMASE ; NEW-DELHI METALLO-BETA-LACTAMASE-1 ; STRUCTURAL BASIS ; ANTIBIOTIC-RESISTANCE ; ACINETOBACTER-BAUMANNII ; CATALYZED-HYDROLYSIS ; CRYSTAL-STRUCTURE ; NDM-1 ; CRYSTALLOGRAPHY ; INHIBITION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203877 |
专题 | 资源环境科学 |
作者单位 | 1.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China; 2.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Hubei, Peoples R China; 3.Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China; 4.Foshan Univ, Sch Stomatol & Med, Foshan 528000, Guangdong, Peoples R China; 5.Third Mil Med Univ, Inst Immunol, Chongqing 400038, Peoples R China |
推荐引用方式 GB/T 7714 | Feng, Han,Liu, Xuehui,Wang, Sheng,et al. The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Feng, Han,Liu, Xuehui,Wang, Sheng,Fleming, Joy,Wang, Da-Cheng,&Liu, Wei.(2017).The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.NATURE COMMUNICATIONS,8. |
MLA | Feng, Han,et al."The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis".NATURE COMMUNICATIONS 8(2017). |
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