Loop motion and base release in purine-specific nucleoside hydrolase: A molecular dynamics study

CORC > 厦门大学 > 化学化工－已发表论文

	Loop motion and base release in purine-specific nucleoside hydrolase: A molecular dynamics study
	Chen, Nanhao ; Ge, Hu ; Xu, Jun ; Cao, Zexing ; Wu, Ruibo ; Cao ZX(曹泽星)
刊名	http://dx.doi.org/10.1016/j.bbapap.2013.02.005
	2013
关键词	TRYPANOSOMA-BRUCEI-BRUCEI SUBSTITUTED IMINORIBITOL DERIVATIVES LEAVING GROUP ACTIVATION STATE ANALOG INHIBITORS PRE-STEADY-STATE TRANSITION-STATE N-RIBOHYDROLASE FORCE-FIELD T. VIVAX MECHANISM
英文摘要	National Science Foundation of China [21203257, 21272289, 21133007]; Ministry of Science and Technology [2011CB808504]; Although various Trypanosoma vivax purine-specific inosine-adenosine-guanosine nucleoside hydrolase (IAG-NH) crystal structures have been determined and the chemical reaction mechanism of substrate hydrolysis has been studied recently, the mechanistic details for the release of base and ribose are still unclear. Herein molecular dynamics (MD) simulations combined with umbrella sampling technique were utilized to explore the regulation mechanisms of key residues and loops I and 2 for the base release. Our results have indicated that the base release process is not the rate-limiting step in the entire hydrolysis process, and the very low barrier of similar to 5.6 kcal/mol can be washed out easily by the notable exothermicity from the substrate hydrolysis step. Moreover, the MD simulations have revealed that Glu82/Trp83 in loop 1 and His247/Arg252 in loop 2 are important to modulate the base release. The partial helix-to-coil change of loop 2 along with the base release process has been observed, showing good agreement with the IAG-NH crystal structures. The local binding site around the ribose after the base release is also discussed. (C) 2013 Elsevier B.V. All rights reserved.
语种	英语
出版者	ELSEVIER SCIENCE BV
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/89021]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Chen, Nanhao,Ge, Hu,Xu, Jun,et al. Loop motion and base release in purine-specific nucleoside hydrolase: A molecular dynamics study[J]. http://dx.doi.org/10.1016/j.bbapap.2013.02.005,2013.
APA	Chen, Nanhao,Ge, Hu,Xu, Jun,Cao, Zexing,Wu, Ruibo,&曹泽星.(2013).Loop motion and base release in purine-specific nucleoside hydrolase: A molecular dynamics study.http://dx.doi.org/10.1016/j.bbapap.2013.02.005.
MLA	Chen, Nanhao,et al."Loop motion and base release in purine-specific nucleoside hydrolase: A molecular dynamics study".http://dx.doi.org/10.1016/j.bbapap.2013.02.005 (2013).