Acta Chimica Sinica ›› 2006, Vol. 64 ›› Issue (22): 2215-2220.     Next Articles

Original Articles

Bcl-2蛋白与Bcl-xL蛋白活性腔比较和底物选择性

郑灿辉, 周有骏*, 朱驹, 陈军, 李耀武, 盛春泉, 宋云龙, 蒋庆锋, 吕加国   

  1. (第二军医大学药学院药物化学教研室 上海 200433)
  • 收稿日期:2006-07-11 修回日期:2006-09-11 出版日期:2006-11-28 发布日期:2006-11-28
  • 通讯作者: 周有骏

Comparison between the Active Sites of Bcl-2 and Bcl-xL Proteins and Their Substrate Binding Selection

ZHENG Can-Hui; ZHOU You-Jun*; ZHU Ju; CHEN Jun; LI Yao-Wu; SHENG Chun-Quan; SONG Yun-Long; JIANG Qing-Feng; LÜ Jia-Guo   

  1. (Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433)
  • Received:2006-07-11 Revised:2006-09-11 Online:2006-11-28 Published:2006-11-28
  • Contact: ZHOU You-Jun

Bcl-2 and Bcl-xL proteins are main members of Bcl-2 protein family, which are new targets of anticancer drugs with bright prospect. These two proteins have similar structure and functions, while differ in many aspects, such as the tumor spectra with high expression of these two proteins, binding selection with other proapoptosis subfamily members, and cell protection function under various apoptosis stimulations. By sequence aligning, structure and surface electrostatic potential comparing of the active sites in Bcl-2 and Bcl-xL proteins, the dominant differences between them are identified. Then the effect of these differences on substrates binding selection is showed by studies of some substrates for example. The result of this paper provides good basis for understanding molecular mechanism of the function difference between Bcl-2 and Bcl-xL proteins, and design, synthesis of small molecule inhibitors with good selection.

Key words: Bcl-2 protein family, sequence alignment, structure comparison, surface electrostatic potential, molecular docking