Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations
文献类型：期刊论文
| 作者 | Sanson, Benoit7,8,9; Colletier, Jacques-Philippe6,7,8,9; Xu, Yechun6 ; Lang, P. Therese5; Jiang, Hualiang4,6; Silman, Israel3; Sussman, Joel L.2; Weik, Martin1,7,8,9
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| 刊名 | PROTEIN SCIENCE
 |
| 出版日期 | 2011-07 |
| 卷号 | 20期号:7页码:1114-1118 |
| 关键词 | acetylcholinesterase X-ray crystallography sub-domain molecular dynamics simulations substrate traffic backdoor |
| ISSN号 | 0961-8368 |
| DOI | 10.1002/pro.661 |
| 文献子类 | Article |
| 英文摘要 | The transient opening of a backdoor in the active-site wall of acetylcholinesterase, one of nature's most rapid enzymes, has been suggested to contribute to the efficient traffic of substrates and products. A crystal structure of Torpedo californica acetylcholinesterase in complex with the peripheral-site inhibitor aflatoxin is now presented, in which a tyrosine at the bottom of the active-site gorge rotates to create a 3.4-angstrom wide exit channel. Molecular dynamics simulations show that the opening can be further enlarged by movement of Trp84. The crystallographic and molecular dynamics simulation data thus point to the interface between Tyr442 and Trp84 as the key element of a backdoor, whose opening permits rapid clearance of catalysis products from the active site. Furthermore, the crystal structure presented provides a novel template for rational design of inhibitors and reactivators, including anti-Alzheimer drugs and antidotes against organophosphate poisoning. |
| WOS关键词 | CRYSTAL-STRUCTURE ; SITE ; DOOR ; FASCICULIN ; COMPLEX ; INHIBITION ; BINDING ; PROTEIN ; GORGE |
| 资助项目 | CEA[00000000] ; CNRS[00000000] ; UJF[00000000] ; Agence Nationale de la Recherche (ANR)[ANR-09-BLAN-0192-04] ; DGA[DGA-REI 2009-34-0023] ; National Natural Science Foundation of China[31050110434] ; State Key Program of Basic Research of China[2009CB918501] ; Computer Network Information Center (CNIC) of the Chinese Academy of Sciences (CAS)[00000000] ; Shanghai Supercomputing Center (SCC) of the CAS[00000000] ; European Commission[031220] ; European Commission[ISSG-CT-2007-037198] ; Kimmelman Center for Biomolecular Structure and Assembly[00000000] ; Benoziyo Center for Neurosciences[00000000] ; Nalvyco Foundation[00000000] ; Bruce Rosen Foundation[00000000] ; Jean and Julia Goldwurm Memorial Foundation[00000000] ; Chinese Academy of Science[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000292257600004 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278491]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Weik, Martin |
| 作者单位 | 1.European Synchrotron Radiat Facil, F-38043 Grenoble, France 2.Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel; 3.Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel; 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 5.Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA; 6.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 7.Univ Grenoble 1, F-38000 Grenoble, France; 8.CNRS, F-38027 Grenoble, France; 9.CEA, Inst Biol Struct, F-38054 Grenoble, France; |
| 推荐引用方式 GB/T 7714 | Sanson, Benoit,Colletier, Jacques-Philippe,Xu, Yechun,et al. Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations[J]. PROTEIN SCIENCE,2011,20(7):1114-1118. |
| APA | Sanson, Benoit.,Colletier, Jacques-Philippe.,Xu, Yechun.,Lang, P. Therese.,Jiang, Hualiang.,...&Weik, Martin.(2011).Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations.PROTEIN SCIENCE,20(7),1114-1118. |
| MLA | Sanson, Benoit,et al."Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations".PROTEIN SCIENCE 20.7(2011):1114-1118. |
入库方式： OAI收割
来源：上海药物研究所
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