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Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors

文献类型：期刊论文

作者Shi, Junyou1,3; Wang, Jinhu4; Liu, Yongjun1,4; Dong, Lihua1,2,3
刊名INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
出版日期2011-11-15
卷号111期号:14页码:3980-3990
关键词Adenosine Kinase (Ak) Inhibitor Conformational Change Molecular Dynamic (Md)
ISSN号0020-7608
文献子类Article
英文摘要Adenosine kinase (AK) is a two-domain protein that catalyzes the phosphorylation of adenosine to adenosine monophosphate. Inhibitors of AK could increase adenosine to levels that activate nearby adenosine receptors and produce a wide variety of therapeutically beneficial activities. To get insight into the interaction mechanism between inhibitors and AK, we chose two kinds of novel inhibitors, alkynylpyrimidine inhibitor (APy) and aryl-nucleoside inhibitor (AN), and used docking and molecular dynamics simulation methods to study the conformational changes of human AK on binding inhibitors. The calculation results revealed that both APy and AN could induce conformational changes of AK and stabilize AK at different semiopen conformations. On binding APy, the small lid-domain rotated 14 degrees, and the binding pocket rearranged after MD simulation. But in AK-AN complex, the rotation of small domain is 22 degrees, and the sugar ring of AN is mobile in the binding pocket. Further docking calculations on APy analogues indicate that the semiopen conformation could well explain the SAR of AK inhibitors. (C) 2010 Wiley Periodicals, Inc. Int J Quantum Chem 111: 3980-3990, 2011; Adenosine kinase (AK) is a two-domain protein that catalyzes the phosphorylation of adenosine to adenosine monophosphate. Inhibitors of AK could increase adenosine to levels that activate nearby adenosine receptors and produce a wide variety of therapeutically beneficial activities. To get insight into the interaction mechanism between inhibitors and AK, we chose two kinds of novel inhibitors, alkynylpyrimidine inhibitor (APy) and aryl-nucleoside inhibitor (AN), and used docking and molecular dynamics simulation methods to study the conformational changes of human AK on binding inhibitors. The calculation results revealed that both APy and AN could induce conformational changes of AK and stabilize AK at different semiopen conformations. On binding APy, the small lid-domain rotated 14 degrees, and the binding pocket rearranged after MD simulation. But in AK-AN complex, the rotation of small domain is 22 degrees, and the sugar ring of AN is mobile in the binding pocket. Further docking calculations on APy analogues indicate that the semiopen conformation could well explain the SAR of AK inhibitors. (C) 2010 Wiley Periodicals, Inc. Int J Quantum Chem 111: 3980-3990, 2011
WOS关键词CRYSTAL-STRUCTURES ; TOXOPLASMA-GONDII ; BIOLOGICAL EVALUATION ; ANGSTROM RESOLUTION ; DOMAIN MOTIONS ; ANALOGS ; BINDING ; ENZYME ; SIMULATION ; RECEPTORS
WOS研究方向Chemistry ; Mathematics ; Physics
语种英语
WOS记录号WOS:000295366300054
公开日期2011-12-13
源URL[http://ir.nwipb.ac.cn//handle/363003/1500]  
专题西北高原生物研究所_中国科学院西北高原生物研究所
作者单位1.Chinese Acad Sci, NW Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China
2.Taishan Med Univ, Sch Chem & Chem Engn, Tai An 271000, Shandong, Peoples R China
3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
4.Shandong Univ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 Shi, Junyou,Wang, Jinhu,Liu, Yongjun,et al. Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors[J]. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,2011,111(14):3980-3990.
APA Shi, Junyou,Wang, Jinhu,Liu, Yongjun,&Dong, Lihua.(2011).Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors.INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,111(14),3980-3990.
MLA Shi, Junyou,et al."Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors".INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 111.14(2011):3980-3990.

入库方式： OAI收割

来源：西北高原生物研究所

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