PGAM1的C端构象变化及功能的计算研究
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- 英文论文题名：A Computational Study of C Terminal Region of Phosphogly cerate Mutase 1
- 论文作者：刘世恩 ; 卢俊彦 ; 蒋华良 ; 周璐 ; 罗成
- 英文论文作者：Shien Liu ; Junyan Lu ; Hualiang Jiang ; Lu Zhou ; Cheng Luo ; Shanghai Institute of Materia Medica ; Chinese Academy of Sciences ; University of Chinese Academy of Sciences ; School of Pharmacy ; Fudan University
- 年：2016
- 作者机构：中国科学院上海药物研究所;中国科学院大学;复旦大学药学院;
- 论文关键词：PGAM1 ; C端 ; 构象变化 ; 副本交换 ; 分子动力学
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
- 语种：中文
- 分类号：Q55
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：145k
- 原文格式：D
- 会议级别：全国
摘要
"Warburg效应"认为有氧糖酵解可能是肿瘤发生的重要因素。人类Phosphoglycerate Mutase 1(PGAM1)是重要的糖代谢酶,在糖酵解/糖异生通路中催化3-phosphoglycerate(3PG)到2-phosphoglycerate(2PG)的转化,2,3-biphosphoglycerate(BPG)作为磷酸的供体和中间物。近来一些研究表明,PGAM1在肿瘤中表达异常增高,抑制PGAM1可以限制肿瘤增长,PGAM1已经成为潜在的肿瘤治疗靶点。本研究使用副本交换分子动力学对PGAM1进行模拟,结果表明C端十分柔性。常规分子动力学模拟进一步证明C端闭合有利于BPG的结合。本研究利用计算的手段详细阐明了C端的柔性,预测利于BPG结合的关键残基,为研究PGAM1在肿瘤发展中的作用提供了线索,同时也为PGAM1及其同源蛋白催化机理、生理功能的研究提供了思路。
The Warburg effect indicates that tumour cells uptake more glucose than normal tissue and favour glycolysis even in the presence of oxygen.Phosphoglycerate Mutase 1(PGAM1),one important enzyme in the glycolytic/gluconeogenic pathways,catalyzes the isomerization between 3-phosphoglycerate(3PG) and2-phosphoglycerate(2PG) with 2,3-biphosphoglycerate(BPG) as a phospho group donor and an intermediate.Several studies demonstrate that PGAMl activity is commonly upregulated in many human cancers and is recognized as a potential therapeutic target of tumour.Herein,a Rexpla Exchange Moleuclar Dynamics simulations of PGAMl was performed and showed that C termimal segment is intrinsically flexibible and can adopt large conformational fluctuations.Classical Molecular Dynamics simulation showed the C terminal segment enclosed the catalytic pocket to assist BPG effective binding.Overall,these results provide essential information to further confirme the role of PGAMl in cancer development and can guide the studies of catalytic mechanism and physiological function on its homologues.
The Warburg effect indicates that tumour cells uptake more glucose than normal tissue and favour glycolysis even in the presence of oxygen.Phosphoglycerate Mutase 1(PGAM1),one important enzyme in the glycolytic/gluconeogenic pathways,catalyzes the isomerization between 3-phosphoglycerate(3PG) and2-phosphoglycerate(2PG) with 2,3-biphosphoglycerate(BPG) as a phospho group donor and an intermediate.Several studies demonstrate that PGAMl activity is commonly upregulated in many human cancers and is recognized as a potential therapeutic target of tumour.Herein,a Rexpla Exchange Moleuclar Dynamics simulations of PGAMl was performed and showed that C termimal segment is intrinsically flexibible and can adopt large conformational fluctuations.Classical Molecular Dynamics simulation showed the C terminal segment enclosed the catalytic pocket to assist BPG effective binding.Overall,these results provide essential information to further confirme the role of PGAMl in cancer development and can guide the studies of catalytic mechanism and physiological function on its homologues.
引文
[1]Walter,R.;Nairn,J.;Duncan,D.;Price,N.Biochem.J.1999,337:89
[2]Hitosugi,T.;Zhou,L.;Elf,S.;Fan,J.Cancer Cell 2012,22:585
[3]Sugita Y.;Okamoto Y.Chem.Phys.Lett.1999,314(1-2):141
[4]Vitalis A.;Pappu R.Annu.Rep.Comput.Chem.2009,5:49
[2]Hitosugi,T.;Zhou,L.;Elf,S.;Fan,J.Cancer Cell 2012,22:585
[3]Sugita Y.;Okamoto Y.Chem.Phys.Lett.1999,314(1-2):141
[4]Vitalis A.;Pappu R.Annu.Rep.Comput.Chem.2009,5:49
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