Bcl-2 protein fusion with bak peptide: Homology modeling analysis
- Author:
Can-Hui ZHENG
1
Author Information
1. Department of Medicinal Chemistry
- Publication Type:Journal Article
- From:
Academic Journal of Second Military Medical University
2006;27(10):1085-1088
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the interactions between Bcl-2 protein, a new target for anticancer agents, and its substrate proteins. Methods: A homologous 3D model of Bcl-2 protein fusing with Bak peptide was established and the reliability of the model was assessed. The active-site cavities of Bcl-2 in the complex and in free state were compared. The key residues and the active sites of Bcl-2 protein for interaction with the substrates were identified, and their fusion with 2 representative inhibitors was analyzed. Results: The constructed complex had a reliable structure. Obvious changes were found in the active sites of Bcl-2 protein in the constructed complex, especially in the regions around α3. The acid and basic residues on the side of active sites and the hydrophobic residues in the bottom of active sites were important for binding with the substrate proteins, which accorded well with the results of biological residue mutation experiments. Conclusion: We have successfully constructed a reliable complex model of Bcl-2 protein binding with Bak peptide.
