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题名: Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation
作者: Zhang, Yuebin1;  Niu, Huiyan2;  Li, Yan1;  Chu, Huiying1;  Shen, Hujun1;  Zhang, Dinglin1;  Li, Guohui1
刊名: SCIENTIFIC REPORTS
发表日期: 2015-02-12
DOI: 10.1038/srep08405
卷: 5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
英文摘要: Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S -> P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S -> P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functional transition from the GK enzyme to the GK domain. Furthermore, the free energy profiles (FEPs) obtained by metadymanics clearly demonstrate that the open-closed conformational transition in WT GK is positive correlated with the process of GMP binding, indicating the GMP-induced closing motion of GK enzyme, which is not observed in the mutant. In addition, the FEPs show that the S -> P mutation can also leads to the mis-recognition of GMP, explaining the vanishing of catalytic activity of the mutant.
关键词[WOS]: MOLECULAR-DYNAMICS SIMULATIONS ;  FREE-ENERGY LANDSCAPE ;  CRYSTAL-STRUCTURE ;  STRUCTURAL BASIS ;  MAGUK FAMILY ;  PDZ DOMAIN ;  MEMBRANE ;  BINDING ;  YEAST ;  PLASTICITY
语种: 英语
WOS记录号: WOS:000349245600004
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/145995
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
2.China Med Univ, Shengjing Hosp, Dept Geriatr, Shenyang 110004, Peoples R China

Recommended Citation:
Zhang, Yuebin,Niu, Huiyan,Li, Yan,et al. Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation[J]. SCIENTIFIC REPORTS,2015,5.
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