Aricept Complexed with Acetylcholinesterase (Chinese): Difference between revisions
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<StructureSection load='1eve' size='450' side='right' scene=' | <StructureSection load='1eve' size='450' side='right' scene='36/362983/1eve_e20_cartoon/1' caption=''> | ||
[[Image:E2020_interactins_in_AChE_gorge.jpg|left|250px]]<br /> | [[Image:E2020_interactins_in_AChE_gorge.jpg|left|250px]]<br /> | ||
'''抗老年痴呆药物安理申（Aricept）与乙酰胆碱酯酶复合物的三维结构''' | '''抗老年痴呆药物安理申（Aricept）与乙酰胆碱酯酶复合物的三维结构''' | ||
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Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs., Kryger G, Silman I, Sussman JL, Structure. 1999 Mar 15;7(3):297-307. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10368299 10368299] | Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs., Kryger G, Silman I, Sussman JL, Structure. 1999 Mar 15;7(3):297-307. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10368299 10368299] | ||
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[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
Latest revision as of 08:47, 25 June 2022
抗老年痴呆药物安理申（Aricept）与乙酰胆碱酯酶复合物的三维结构 背景介绍部分乙酰胆碱酯酶的抑制剂已用于老年痴呆疾病的治疗或正处于临床研究阶段。 E2020, 商品名为安理申, 属于1-苄基-4-哌啶类乙酰胆碱酯酶（acetylcholinesterase）抑制剂。该抑制剂由日本的Eisai公司研发成功。此类抑制剂是在加利福尼亚电鳐乙酰胆碱酯酶三维结构(1ea5)的解析之前，基于定量构效关系研究而设计改造获得的。动物模型研究表明E2020能有效改善胆碱能功能减退。E2020与乙酰胆碱酯酶的结合力非常强，其与电鳐和老鼠乙酰胆碱酯酶的结合常数在纳摩尔级。 结果E2020与乙酰胆碱酯酶复合物的晶体结构表明E2020采用了结合于乙酰胆碱酯酶，其结合部位从乙酰胆碱酯酶活性口袋底部的阴离子结合位点的一直延伸口袋顶部外周阴离子结合位点的附近。但是，E2020并不直接与酶的催化三联体或者氧离子空穴相互作用，而是通过与其间接作用。 结论晶体结构表明E2020的设计充分考虑了乙酰胆碱酯酶狭长活性口袋的多个重要特征，从而使该药物与乙酰胆碱酯酶的结合力非常强，同时对乙酰胆碱酯酶的选择性结合远远高于丁酰胆碱酯酶。此外，该复合物的晶体结构还提供了进一步改造E2020的信息，如从三维结构中看到活性口袋中仍有空隙，可以通过改造E2020从而使小分子与乙酰胆碱酯酶的结合更加充分。 关于这个结构PBD编码1EVE是单个蛋白质（其序列来自加利福尼亚电鳐（Torpedo_californica）的乙酰胆碱酯酶） 与多糖和配体E20的复合物结构。乙酰胆碱酯酶（Acetylcholinesterase），其酶学命名号为EC 3.1.1.7。 所有关于这个结构的信息可以从OCA获得。 |
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参考文献参考文献
Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs., Kryger G, Silman I, Sussman JL, Structure. 1999 Mar 15;7(3):297-307. PMID:10368299