Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding
文献类型：期刊论文
| 作者 | Wu, Yan3; Qin, Guangrong1; Gao, Feng4; Liu, Yue3; Vavricka, Christopher J.2,3; Qi, Jianxun3; Jiang, Hualiang1 ; Yu, Kunqian1; Gao, George F.2,3
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2013-03-27 |
| 卷号 | 3 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep01551 |
| 文献子类 | Article |
| 英文摘要 | The recently discovered 150-cavity (formed by loop residues 147-152, N2 numbering) adjacent to the enzymatic active site of group 1 influenza A neuraminidase (NA) has introduced a novel target for the design of next-generation NA inhibitors. However, only group 1 NAs, with the exception of the 2009 pandemic H1N1 NA, possess a 150-cavity, and no 150-cavity has been observed in group 2 NAs. The role of the 150-cavity played in enzymatic activity and inhibitor binding is not well understood. Here, we demonstrate for the first time that oseltamivir carboxylate can induce opening of the rigid closed N2 150-loop and provide a novel mechanism for 150-loop movement using molecular dynamics simulations. Our results provide the structural and biophysical basis of the open form of 150-loop and illustrates that the inherent flexibility and the ligand induced flexibility of the 150-loop should be taken into consideration for future drug design. |
| WOS关键词 | PARTICLE MESH EWALD ; A H3N2 VIRUS ; MAXIMUM-LIKELIHOOD ; H1N1 NEURAMINIDASE ; DRUG DESIGN ; HEMAGGLUTININ ; 150-CAVITY ; TRANSMISSION ; OSELTAMIVIR ; SIALIDASE |
| 资助项目 | China Ministry of Science and Technology (MOST)[2011CB504703] ; China Ministry of Science and Technology (MOST)[2009CB918502] ; National High Technology Research and Development Program of China (863 Program)[2012AA020301] ; National High Technology Research and Development Program of China (863 Program)[2012AA01A305] ; China National Grand S&T Special Project[2013ZX10004611] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; Innovative Research Group of the National Natural Science Foundation of China (NSFC)[81021003] ; Chinese Academy of Sciences[2011Y2SA01] ; NSFC[31150110147] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000316722500001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277688]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yu, Kunqian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Beijing Inst Life Sci, RNIH, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China; 4.Chinese Acad Sci, Inst Biophys, Lab Noncoding RNA, Beijing 100101, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wu, Yan,Qin, Guangrong,Gao, Feng,et al. Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding[J]. SCIENTIFIC REPORTS,2013,3. |
| APA | Wu, Yan.,Qin, Guangrong.,Gao, Feng.,Liu, Yue.,Vavricka, Christopher J..,...&Gao, George F..(2013).Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding.SCIENTIFIC REPORTS,3. |
| MLA | Wu, Yan,et al."Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding".SCIENTIFIC REPORTS 3(2013). |
入库方式： OAI收割
来源：上海药物研究所
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