Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors | |
| Dong, Lihua1,2,3; Shi, Junyou1,3; Wang, Jinhu4; Liu, Yongjun1,4 | |
| 2011-11-15 | |
| 发表期刊 | INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
 |
| ISSN | 0020-7608 |
| 卷号 | 111期号:14页码:3980-3990 |
| 文章类型 | Article |
| 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 |
| 关键词 | Adenosine Kinase (Ak) Inhibitor Conformational Change Molecular Dynamic (Md) |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 关键词[WOS] | CRYSTAL-STRUCTURES ; TOXOPLASMA-GONDII ; BIOLOGICAL EVALUATION ; ANGSTROM RESOLUTION ; DOMAIN MOTIONS ; ANALOGS ; BINDING ; ENZYME ; SIMULATION ; RECEPTORS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Chemistry ; Mathematics ; Physics |
| WOS类目 | Chemistry, Physical ; Mathematics, Interdisciplinary Applications ; Physics, Atomic, Molecular & Chemical |
| WOS记录号 | WOS:000295366300054 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://210.75.249.4/handle/363003/1500 |
| 专题 | 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 | Dong, Lihua,Shi, Junyou,Wang, Jinhu,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 | Dong, Lihua,Shi, Junyou,Wang, Jinhu,&Liu, Yongjun.(2011).Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors.INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,111(14),3980-3990. |
| MLA | Dong, Lihua,et al."Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors".INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 111.14(2011):3980-3990. |
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