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化学学报
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化学学报 ›› 2005, Vol. 63 ›› Issue (9): 809-813. 上一篇    下一篇

研究论文

CDK4与靛玉红及其衍生物复合物结构的模建

张娜，蒋勇军*，邹建卫，曾敏，胡桂香，俞庆森   

  1. (浙江大学宁波理工学院 分子设计与营养工程市重点实验室 宁波 315104)
  • 投稿日期:2004-07-05 修回日期:2005-01-07 发布日期:2010-12-10
  • 通讯作者: 蒋勇军

Molecular Models of Cyclin-dependent Kinase 4 Complexed with Indirubin and Its Analogues

ZHANG Na, JIANG Yong-Jun*, ZOU Jian-Wei, ZENG Min, HU Gui-Xiang, YU Qing-Sen   

  1. (Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo Institute of Technology,
    Zhejiang University, Ningbo 315104)
  • Received:2004-07-05 Revised:2005-01-07 Published:2010-12-10
  • Contact: JIANG Yong-Jun

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被引次数

33 | 6

细胞周期蛋白依赖性激酶(Cyclin-dependent Kinases, CDKs)是细胞周期调控的重要因子, 也是治疗癌症的一类重要的药物靶标. 靛玉红是传统中药当归龙荟丸中治疗慢性疾病的有效成分, 靛玉红及其衍生物5-磺酸基-靛玉红对CDKs具有有效的抑制作用. 以获得晶体结构的CDK2与5-磺酸根-靛玉红的复合物为模板, 通过同源模建和分子对接的方法构建出的CDK4与靛玉红及其衍生物的结合模式. 结合CDK4与两种抑制剂的复合物结构, 解释了靛玉红和衍生物5-磺酸基-靛玉红之间抑制活性的差别, 同时也分析了5-磺酸基-靛玉红对CDK2和CDK4不同选择性的原因. 所建CDK4结构为进一步进行基于结构的抗癌药物设计提供了合理的模型.

关键词: CDK, 靛玉红, 同源模建, 分子对接, 抗癌药物

Indirubin and its analogue, indirubin-5-sulphonic acid, have shown potent ability to inhibit cyclin-dependent-kinases (CDKs). Using the crystal structure of CDK2 complexed with indirubin-5- sulphonate as the template, models of CDK4 complexed with indirubin and its analogue were built by homology modeling and molecular docking. The structure comparisons of CDK4 with indirubin and its analogue could explain different inhibition ability. Moreover, the different activity of indirubin-5-sulphonic acid complexed with CDK2 and CDK4 was also illustrated. The model structure provided the basis for designing more potent anticancer drug.

Key words: cyclin-dependent-kinase, indirubin, homology modeling, molecular docking, anticancer