物理化学学报 >> 2009, Vol. 25 >> Issue (04): 635-639.doi: 10.3866/PKU.WHXB20090405

研究论文 上一篇    下一篇

分子动力学模拟方法研究结构水在糖原合成酶激酶-3β中的作用

孙浩 蒋勇军 俞庆森 邹建卫   

  1. 浙江大学化学系, 杭州 310027; 浙江大学宁波理工学院分子设计与营养工程重点实验室, 浙江 宁波 315100
  • 收稿日期:2008-11-27 修回日期:2009-01-07 发布日期:2009-03-31
  • 通讯作者: 蒋勇军 E-mail:yjjiang@nit.zju.edu.cn

Molecular Dynamics Simulation of Significant Roles of Structural Water Molecules in Glycogen Synthase Kinase-3β

 SUN Hao, JIANG Yong-Jun, YU Qing-Sen, ZOU Jian-Wei   

  1. Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China; Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100, Zhejiang Province, P. R. China
  • Received:2008-11-27 Revised:2009-01-07 Published:2009-03-31
  • Contact: JIANG Yong-Jun E-mail:yjjiang@nit.zju.edu.cn

摘要:

用分子动力学模拟的方法揭示了结构水分子在糖原合成酶激酶-3β(GSK-3β)中的作用. 如果没有结构水, ATP嘌呤环的结合位置将发生偏移以填补结构水留下的空间; ATP结合口袋中的氢键网络将被破坏, 保守残基Lys85与ATP的磷酸根侧链只能形成一个保守氢键, 无法维持磷酸根转移所需的线性关系; 由于失去了氢键网络的稳定作用, Glu97和Lys85会向远离ATP的方向移动, 并导致Arg96的侧链发生偏转, 使Arg96无法保持与Arg180和Lys205之间正常的相对位置, 最终影响GSK-3β与底物的结合.

关键词: 糖原合成酶激酶-3β, 结构水分子, 分子动力学模拟

Abstract:

In this paper, we illustrate the significant role of structural water in GSK-3βusing a dynamic simulation. We find that without structural water, the adenine moiety of ATP will drift from its correct position and prevent the formation of a H-bonding network. Conserved Lys85 can only form one H-bond with ATP and the in-line phosphoryl transfer mechanism would probably be destroyed. Glu97 and Lys85 are removed from ATP and the side chain of Arg96 will turn away, which can prevent substrate binding.

Key words: Glycogen synthase kinase-3β, Structural water molecule, Molecular dynamics simulation

MSC2000: 

  • O641