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

NWIPB OpenIR

	Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors
	Dong, Lihua ; Shi, Junyou ; Wang, Jinhu ; Liu, Yongjun
	2011-11-15
发表期刊	INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY ; Dong, LH; Shi, JY; Wang, JH; Liu, YJ.Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors,INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,2011,111(14):3980-3990
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
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/50970
专题	中国科学院西北高原生物研究所
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, Dong, LH; Shi, JY; Wang, JH; Liu, YJ.Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors,INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,2011,111(14):3980-3990,2011.
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.
MLA	Dong, Lihua,et al."Theoretical Studies on the Conformational Change of Adenosine Kinase Induced by Inhibitors".INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY (2011).