高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (12): 2708.doi: 10.7503/cjcu20120319

• 物理化学 • 上一篇    下一篇

氨基酸突变对GABAa受体结合能力的影响

温夏夏1, 南士滨1, 黄迎2, 任天瑞1, 姚建华2   

  1. 1. 上海师范大学生命与环境科学学院, 资源化学教育部重点实验室, 上海 200234;
    2. 中国科学院上海有机化学研究所, 上海 200032
  • 收稿日期:2012-04-09 出版日期:2012-12-10 发布日期:2012-11-20
  • 通讯作者: 任天瑞,男,博士,教授,博士生导师,主要从事农药靶标研究.E-mail:trren@shnu.edu.cn姚建华,女,博士,研究员,博士生导师,主要从事化学信息学方法应用研究.E-mail:yaojh@mail.sioc.ac.cn E-mail:trren@shnu.edu.cn;yaojh@mail.sioc.ac.cn
  • 基金资助:

    国家科技部"十二五"支撑项目(批准号: 2011BAE06B05)、国家"九七三"计划项目(批准号: 2010CB126106)、 国家自然科学基金(批准号: 21172147和21072216)和上海市教委创新项目(批准号: 11ZZ112)资助.

Studies of Interaction Between GABA and Mutant GABAaR

WEN Xia-Xia1, NAN Shi-Bin1, HUANG Ying2, REN Tian-Rui1, YAO Jian-Hua2   

  1. 1. Key Laboratory of Resource Chemistry, Ministry of Education, College of Life and Environment Science, Shanghai Normal University, Shanghai 200234, China;
    2. Shanghai Institute of Organic Chemistry, Chinese Academy Sciences, Shanghai 200032, China
  • Received:2012-04-09 Online:2012-12-10 Published:2012-11-20
  • Contact: Tian-Rui REN E-mail:trren@shnu.edu.cn;yaojh@mail.sioc.ac.cn

PDF (PC)

被引次数

3

摘要：

采用同源建模技术构建了大鼠γ-氨基丁酸a型受体(GABAaR)模型, 并将氨基酸残基β157Tyr和β205Tyr突变为相应的突变受体模型. 使用分子对接方法计算了γ-氨基丁酸(GABA)与突变前后受体的相互作用. 对接计算结果显示, Tyr突变为Phe后, 两种突变受体的对接能量大幅提高, GABA生物活性降低; 当Phe的对位引入氟原子后, 对接能量与未突变受体相比更低. 另外, 与β205Tyr突变相比, 与配体距离较近的β157Tyr突变, 对受体与配体作用的影响更大.

关键词: γ-氨基丁酸a型受体, 同源建模, 氨基酸突变, 活性位点, 分子对接

Abstract:

Homology modeling and docking are important technologies in computer-aided drug design, which can explain the interactions between ligands and receptors. In this study, a rat γ-aminobutyric acid a-type receptor(GABAaR) model and its β205Tyr and β157Tyr mutant receptor models were built by homology modeling. The interactions between γ-aminobutyric acid(GABA) and the GABAaR and its mutants were studied by molecular docking, and the result show that the docking energy of the mutant receptors increases significantily and the biological activity of GABA decreases when Tyr changes to Phe; the docking energy becomes lower than that of the original receptor when Tyr changes to 4-F-Phe. In addition, the impact of β157Tyr mutations on the interaction between receptors and ligands is much more striking than that of β205Tyr when β157Tyr is closer to the ligand.

Key words: γ-Aminobutyric acid a-type receptor, Homology modeling, Amino acid mutation, Active site, Molecular docking

中图分类号: 

TrendMD: