Aricept Complexed with Acetylcholinesterase (Chinese)
From Proteopedia
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| + | <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 /> | ||
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| - | {{STRUCTURE_1eve| PDB=1eve | SCENE=Main_Page/E2020_in_ache_spinning/1 }} | ||
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'''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''' | ||
==背景介绍== | ==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。 | 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。 | ||
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| + | {{Clear}} | ||
==结果== | ==结果== | ||
| - | E2020与乙酰胆碱酯酶复合物的晶体结构表明E2020采用了<scene name='1eve/E2020_close_up_with_84_279/ | + | E2020与乙酰胆碱酯酶复合物的晶体结构表明E2020采用了<scene name='1eve/E2020_close_up_with_84_279/13'>非常独特的取向</scene>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<scene name='1eve/E2020_close_up_with_84lbld/7'>残基W84</scene>一直延伸口袋顶部外周阴离子结合位点的<scene name='1eve/E2020_close_up_with_84_279lbld/5'>残基W279</scene>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<scene name='1eve/E20_interactionshown/8'>溶剂水分子</scene>与其间接作用。 |
==结论== | ==结论== | ||
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PBD编码1EVE是单个[http://en.wikipedia.org/wiki/Protein 蛋白质]（其序列来自加利福尼亚电鳐（[http://en.wikipedia.org/wiki/Torpedo_californica Torpedo_californica]）的乙酰胆碱酯酶） | PBD编码1EVE是单个[http://en.wikipedia.org/wiki/Protein 蛋白质]（其序列来自加利福尼亚电鳐（[http://en.wikipedia.org/wiki/Torpedo_californica Torpedo_californica]）的乙酰胆碱酯酶） | ||
与多糖和[http://en.wikipedia.org/wiki/ligands 配体]E20的复合物结构。乙酰胆碱酯酶（[[Acetylcholinesterase]]），其酶学命名号为[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 EC 3.1.1.7]。 所有关于这个结构的信息可以从[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EVE OCA]获得。 | 与多糖和[http://en.wikipedia.org/wiki/ligands 配体]E20的复合物结构。乙酰胆碱酯酶（[[Acetylcholinesterase]]），其酶学命名号为[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 EC 3.1.1.7]。 所有关于这个结构的信息可以从[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EVE OCA]获得。 | ||
| - | + | </StructureSection> | |
==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:[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] | ||
| - | + | [[ar:Aricept_Complexed_with_Acetylcholinesterase (Arabic)]] | |
| + | [[ca:Aricept_Complexed_with_Acetylcholinesterase (Catalan)]] | ||
| + | [[zh:Aricept_Complexed_with_Acetylcholinesterase (Chinese)]] | ||
| + | [[cs:Aricept_Complexed_with_Acetylcholinesterase (Czech)]] | ||
| + | [[de:Aricept_Complexed_with_Acetylcholinesterase (German)]] | ||
| + | [[en:Aricept_Complexed_with_Acetylcholinesterase]] | ||
| + | [[es:Aricept_Complexed_with_Acetylcholinesterase (Spanish)]] | ||
| + | [[fr:Aricept_Complexed_with_Acetylcholinesterase (French)]] | ||
| + | [[he:Aricept_Complexed_with_Acetylcholinesterase (Hebrew)]] | ||
| + | [[it:Aricept_Complexed_with_Acetylcholinesterase (Italian)]] | ||
| + | [[ru:Aricept_Complexed_with_Acetylcholinesterase (Russian)]] | ||
| + | [[sk:Aricept_Complexed_with_Acetylcholinesterase (Slovak)]] | ||
| + | [[vi:Aricept_Complexed_with_Acetylcholinesterase (Vietnamese)]] | ||
| + | [[tr:Aricept_Complexed_with_Acetylcholinesterase (Turkish)]] | ||
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[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: neurotransmitter cleavage]] | [[Category: neurotransmitter cleavage]] | ||
[[Category: serine hydrolase]] | [[Category: serine hydrolase]] | ||
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov 8 12:39:55 2007'' | ||
Current revision
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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
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Joel L. Sussman, Alexander Berchansky, Jaime Prilusky, Yechun Xu, Eran Hodis, Fred Vellieux
