Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation

	Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation
	Zhang, Yuebin 1; Niu, Huiyan 2; Li, Yan 1; Chu, Huiying 1; Shen, Hujun 1; Zhang, Dinglin 1; Li, Guohui 1
刊名	scientific reports
	2015-02-12
卷号	5
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.
WOS标题词	science & technology
类目[WOS]	multidisciplinary sciences
研究领域[WOS]	science & technology - other topics
关键词[WOS]	molecular-dynamics simulations ; free-energy landscape ; crystal-structure ; structural basis ; maguk family ; pdz domain ; membrane ; binding ; yeast ; plasticity
收录类别	SCI
语种	英语
WOS记录号	WOS:000349245600004
公开日期	2016-05-09
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/145995]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
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
推荐引用方式 GB/T 7714	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.
APA	Zhang, Yuebin.,Niu, Huiyan.,Li, Yan.,Chu, Huiying.,Shen, Hujun.,...&Li, Guohui.(2015).Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation.scientific reports,5.
MLA	Zhang, Yuebin,et al."Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation".scientific reports 5(2015).