IHEP OpenIR  > 多学科研究中心
Mechanism of flexibility control for ATP access of hepatitis C virus NS3 helicase
Palla, M; Chen, CP; Zhang, Y; Li, JY; Ju, JY; Liao, JC;李敬源
2013
发表期刊JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷号31期号:2页码:129-141
摘要Hepatitis C virus (HCV) NS3 helicase couples adenosine triphosphate (ATP) binding and hydrolysis to polynucleotide unwinding. Understanding the regulation mechanism of ATP binding will facilitate targeting of the ATP-binding site for potential therapeutic development for hepatitis C. T324, an amino acid residue connecting domains 1 and 2 of NS3 helicase, has been suggested as part of a flexible hinge for opening of the ATP-binding cleft, although the detailed mechanism remains largely unclear. We used computational simulation to examine the mutational effect of T324 on the dynamics of the ATP-binding site. A mutant model, T324A, of the NS3 helicase apo structure was created and energy was minimized. Molecular dynamics simulation was conducted for both wild type and the T324A mutant apo structures to compare their differences. For the mutant structure, histogram analysis of pairwise distances between residues in domains 1 and 2 (E291-Q460, K210-R464 and R467-T212) showed that separation between the two domains was reduced by 10% and the standard deviation by 33%. Root mean square fluctuation (RMSF) analysis demonstrated that residues in close proximity to residue 324 have at least 30% RMSF value reductions in the mutant structure. Solvent RMSF analysis showed that more water molecules were trapped near D290 and H293 in domain 1 to form an extensive interaction network constraining cleft opening. We also demonstrated that the T324A mutation established a new atomic interaction with V331, revealing that an atomic interaction cascade from T324 to residues in domains 1 and 2 controls the flexibility of the ATP-binding cleft.
关键词molecular dynamics simulation ATP-binding cleft pairwise distance analysis RMSF analysis hinge motion
学科领域Biochemistry & Molecular Biology; Biophysics
DOI10.1080/07391102.2012.698236
收录类别SCI
WOS记录号WOS:000313642100001
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/223859
专题多学科研究中心
推荐引用方式
GB/T 7714
Palla, M,Chen, CP,Zhang, Y,et al. Mechanism of flexibility control for ATP access of hepatitis C virus NS3 helicase[J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,2013,31(2):129-141.
APA Palla, M,Chen, CP,Zhang, Y,Li, JY,Ju, JY,&Liao, JC;李敬源.(2013).Mechanism of flexibility control for ATP access of hepatitis C virus NS3 helicase.JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,31(2),129-141.
MLA Palla, M,et al."Mechanism of flexibility control for ATP access of hepatitis C virus NS3 helicase".JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 31.2(2013):129-141.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
1450.pdf(601KB)期刊论文作者接受稿限制开放CC BY-NC-SA请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Palla, M]的文章
[Chen, CP]的文章
[Zhang, Y]的文章
百度学术
百度学术中相似的文章
[Palla, M]的文章
[Chen, CP]的文章
[Zhang, Y]的文章
必应学术
必应学术中相似的文章
[Palla, M]的文章
[Chen, CP]的文章
[Zhang, Y]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。