高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (05): 996.doi: 10.3969/j.issn.0251-0790.2012.05.023

• 生物化学 • 上一篇    下一篇

猪伪狂犬病毒胸苷激酶的三维结构模建与配体设计

王印1,2, 杨泽晓1,2, 姚学萍1   

  1. 1. 四川农业大学动物医学院, 雅安 625014;
    2. 四川农业大学动物疫病与人类健康四川省重点实验室, 雅安 625014
  • 收稿日期:2011-06-07 出版日期:2012-05-10 发布日期:2012-05-10
  • 作者简介:王 印, 男, 博士, 教授, 博士生导师, 主要从事动物疫病防治和动物检疫研究. E-mail: 704029604@qq.com
  • 基金资助:

    教育部"长江学者和创新团队发展计划"创新团队项目(批准号: IRT 0848)和"十一五"国家支撑计划重点项目(批准号: 2010DAD04B03)资助.

Modeling of 3D Structure of Pseudorabies Virus(PRV) Thymidine Kinase and Its Ligand Designing

WANG Yin1,2, YANG Ze-Xiao1,2, YAO Xue-Ping1   

  1. 1. College of Veterinary Medicine, Sichuan Agricultural University, Yaan 625014, China;
    2. Key Laboratory of Animal Disease and Human Health of Sichuan Province, Yaan 625014, China
  • Received:2011-06-07 Online:2012-05-10 Published:2012-05-10

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被引次数

3

摘要： 以伪狂犬病毒(PRV)Fa为材料, 克隆测序胸苷激酶(TK)基因, 采用同源模建方法构建胸苷激酶的三维结构模型, 并经Ramachandran图和Profile_3D图验证了模型的可靠性. 采用InsightⅡ/Binding site, Delphi和Affinity方法定位了胸苷激酶的活性位点Site 1, 在此基础上设计出胸苷激酶抑制小分子N-苯基-N'-甲基脲, 通过柔性分子对接法阐明了胸苷激酶抑制剂与靶酶活性位点的相互作用模式, 发现模式中特异性的氢键相互作用可能是对靶酶产生抑制活性的重要分子基础. 研究结果为合理设计PRV胸苷激酶抑制剂, 探索新的治疗及预防伪狂犬病方案奠定了基础.

关键词: 伪狂犬病毒, 胸苷激酶, 同源模建, 分子动力学

Abstract: To research the methods for the prevention and control of pseudorabies virus(PRV), the thymidine kinase(TK) gene of PRV was amplified with PRV DNA as the template by PCR, and cloned into pMD18-T Vector, sequenced and translated into the amino acid sequence of TK using DNAStar software. Then the three-dimensional(3D) structure mode of TK was constructed by the homology modeling method, and the model reliability was determined by both Ramachandran plot and Profile-3D image. InsightⅡ/Binding site, Delphi and Affinity modules were used to explore the possible functional sites and interaction model of the TK and its inhibitor. The results show that Site 1 are the possible active sites and a new low molecular inhibitor, N-phenyl-N'-methylurea, is designed, and the special hydrogen-band interaction may play an important role in inhibiting the enzyme activity. These results may provide new theoretical references and pathway through PRV-TK inhibitors designing to the study of methods of PRV control.

Key words: Pseudorabies virus(PRV), Thymidine kinase(TK), Homology modeling, Molecular dynamics

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