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作者

Lihua Dong Junyou Shi Jinhu Wang Yongjun Liu

作者单位

School of Chemistry and Chemical Engineering, Taishan Medical University, Taian, Shandong 271000, China Graduate University of Chinese Academy of Science, Beijing 100049, China Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China

刊名

International Journal of Quantum Chemistry

年份

2011

卷号

Vol.111 No.14

页码

3980-3990

ISSN

0020-7608

关键词

adenosine kinase (AK) inhibitor conformational change molecular dynamic (MD)

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 dy...更多

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°, and the binding pocket rearranged after MD simulation. But in AK-AN complex, the rotation of small domain is 22°, 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.收起

学科

【SCI学科】CHEMISTRY, PHYSICAL;MATHEMATICS, INTERDISCIPLINARY APPLICATIONS;PHYSICS, ATOMIC, MOLECULAR & CHEMICAL 【ESI学科】CHEMISTRY

影响因子

2016年:2.92;2015年:2.184;2014年:1.432;2013年:1.166;2012年:1.306

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