物理化学学报 >> 2009, Vol. 25 >> Issue (07): 1290-1296.doi: 10.3866/PKU.WHXB20090701

研究论文 上一篇    下一篇

牛视紫红质蛋白质中视黄醛的活性位点

徐四川, 邓圣荣, 马丽英, 史强, 葛茂发, 张兴康   

  1. 云南大学化学科学与工程技术学院生命起源研究室, 自然资源药物化学教育部重点实验室, 昆明 650091|中国科学院化学研究所, 北京分子科学国家实验室, 分子动态与稳态结构国家重点实验室, 北京 100190
  • 收稿日期:2009-01-12 修回日期:2009-03-18 发布日期:2009-06-26
  • 通讯作者: 徐四川, 史强 E-mail:sichuan@ynu.edu.cn; qshi@iccas.ac.cn

Active Sites for Retinal Binding to Bovine Rhodopsin

XU Si-Chuan, DENG Sheng-Rong, MA Li-Ying, SHI Qiang, GE Mao-Fa, ZHANG Xing-Kang   

  1. Key Laboratory for Medicinal Chemistry of Natural Resource, Ministry of Education, Laboratory on the Origin of Life, College of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China|State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
  • Received:2009-01-12 Revised:2009-03-18 Published:2009-06-26
  • Contact: XU Si-Chuan, SHI Qiang E-mail:sichuan@ynu.edu.cn; qshi@iccas.ac.cn

摘要:

视紫红质蛋白是一个跨膜蛋白, 视黄醛(RET)在该蛋白中的活性结合位点涉及到视觉过程机理, 与一些眼科疾病病理有关. 基于牛视紫红质蛋白1U19的蛋白质晶体结构数据, 采用密度泛函理论的B3LYP方法计算RET-Lys296残基与视黄醛分子周围半径为0.6 nm的空间范围30个氨基酸残基相互作用和结合能. 数值显示1U19蛋白中的残基Glu113、Glu181和Glu122是质子化的RET-Lys296残基的活性结合位点, 结合能分别为-333.38、-205.67和-194.56 kJ·mol-1. 这些氨基酸残基带有一个负电荷, 与质子化的RET-Lys296残基发生强烈的离子静电相互作用. 另外几个残基Ala292、Cys187、Phe293、Pro291以及Trp265等与质子化RET-Lys296残基也有相互吸引作用. 当RET-Lys296残基非质子化, 上述相互作用消失, 促使视黄醛分子与视蛋白分离. 研究发现残基Glu113和Glu181周围各自有一个结晶水分子通过双氢键形式起着稳定作用.

关键词: 视紫红质, 视黄醛, 1U19, 活性位点, 密度泛函理论

Abstract:

Rhodopsin is a membrane protein and its retinal (RET) active binding sites are related to the process of vision and the pathology of some ophthalmic ailments. Based on the bovine rhodopsin crystal structure (PDB code: 1U19), computations were performed using density functional theory to explore the interaction and binding energies between the RET-Lys296 residue and each of the 30 amino acid residues arranged in a sphere with 0.6 nm radius around a RET molecule. Results show that Glu113, Glu181 and Glu122 residues are the active binding sites for the protonated RET-Lys296 residue and that their binding energies are -333.38, -205.67 and -194.56 kJ·mol-1, respectively. They each have one negative charge to interact with the protonated RET-Lys296 residue through a strong electrostatic interaction. Other residues Ala292, Cys187, Phe293, Pro291 and Trp265 have smaller binding energies with the protonated RET-Lys296 residue at the 1U19 protein. When the RET-Lys296 residue is deprotonated, the interactions mentioned above disappear therefore to promote the dissociation of retinal from rhodopsin. Our results demonstrate that two crystal H2O molecules that form hydrogen bonds to Glu113 and Glu181 residues also play an important role in stabilizing the RET-Lys296 residue.

Key words: Rhodopsin, Retinal, 1U19, Active site, Density functional theory

MSC2000: 

  • O641