Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions

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	Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions
	Gao, Kaifu 1; He, Hongqing1 ; Yang, Minghui 1; Yan, Honggao 2
刊名	BIOCHEMISTRY
	2015-11-10
卷号	54 期号:44 页码:6734-6742
英文摘要	6-Hydroxymethy1-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the first reaction in the folate biosynthetic pathway. Comparison of its X-ray and nuclear magnetic resonance structures suggests that the enzyme undergoes significant conformational change upon binding to its substrates, especially in three catalytic loops. Experimental research has shown that even when confined by crystal contacts, loops 2 and 3 remain rather flexible when the enzyme is in its apo form, raising questions about the putative large-scale induced-fit conformational change of HPPK. To investigate the loop dynamics in a crystal-free environment, we performed conventional molecular dynamics simulations of the apo-enzyme at two different temperatures (300 and 350 K). Our simulations show that the crystallographic B-factors considerably underestimate the loop dynamics; multiple conformations of loops 2 and 3, including the open, semi-open, and closed conformations that an enzyme must adopt throughout its catalytic cycle, are all accessible to the apo-enzyme. These results revise our previous view of the functional mechanism of conformational change upon MgATP binding and offer valuable structural insights into the workings of HPPK In this paper, conformational network analysis and principal component analysis related to the loops are discussed to support the presented conclusions.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology
研究领域[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	NORMAL-MODE ANALYSIS ; 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN PYROPHOSPHOKINASE ; INDUCED-FIT ; PROTEIN DYNAMICS ; PRINCIPAL COMPONENT ; CRYSTAL-STRUCTURE ; BINDING ; SELECTION ; MECHANISM ; MOTIONS
收录类别	SCI
语种	英语
WOS记录号	WOS:000364614500009
公开日期	2015-12-22
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/9052]
专题	武汉物理与数学研究所_理论与交叉研究部
作者单位	1.Chinese Acad Sci, Wuhan Inst Phys & Math, Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 2.Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA
推荐引用方式 GB/T 7714	Gao, Kaifu,He, Hongqing,Yang, Minghui,et al. Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions[J]. BIOCHEMISTRY,2015,54(44):6734-6742.
APA	Gao, Kaifu,He, Hongqing,Yang, Minghui,&Yan, Honggao.(2015).Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions.BIOCHEMISTRY,54(44),6734-6742.
MLA	Gao, Kaifu,et al."Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions".BIOCHEMISTRY 54.44(2015):6734-6742.