Molecular Dynamics Simulations of the Escherichia coli HPPK Apoenzyme Reveal a Network of Conformational Transitions
文献类型：期刊论文
| 作者 | Gao, Kaifu1; He, Hongqing1 ; Yang, Minghui1; Yan, Honggao2
|
| 刊名 | BIOCHEMISTRY
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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