Research Article Open Access

Prediction of a Putative Functional Region in the Human Bax Protein by Computational Analysis

María Sánchez-Aguilar1, Laurence A. Marchat1 and Absalom Zamorano1
  • 1 Institutional Program of Molecular Biomedicine, Mexico

Abstract

Structural domains are relevant elements for interactions between Bcl-2 family members to regulate apoptosis and cell survival. Although BH1-BH4 domains can be identified by their sequence and selective occurrence in Bcl-2-family members, structural regions have not been entirely determined yet. The functional residues of Bax, the most representative pro-apoptotic protein of the human Bcl-2 family, remain almost unknown. Here, we identified the human Bax homologues through PSI-Blast analysis. By phylogenetic study, protein sequence multialignment and three-dimensional mapping, we detected the most conserved amino acids in these proteins. Based on these results, we predicted that the human Bax protein has a putative functional region formed by ten relevant residues in BH1 (G103, N106, G108, R109, V111 and A112) and BH2 domains (W151, G157 and W158), as well as outside of them (V95). Interestingly, the structural analysis of this functional region showed that these residues are closely located inside the protein, forming a putative active site. Moreover, this site seems to be protected by the C-terminal end α9 helix that could act as a regulating gate for the access to this region. In addition, the hydrophobic feature of this helix suggests that it could be involved in the insertion into the mitochondrial membrane that is thought to be important for Bcl-2 family members dimerization and activation.

American Journal of Infectious Diseases
Volume 3 No. 2, 2007, 68-75

DOI: https://doi.org/10.3844/ajidsp.2007.68.75

Submitted On: 16 March 2007 Published On: 30 June 2007

How to Cite: Sánchez-Aguilar, M., Marchat, L. A. & Zamorano, A. (2007). Prediction of a Putative Functional Region in the Human Bax Protein by Computational Analysis. American Journal of Infectious Diseases, 3(2), 68-75. https://doi.org/10.3844/ajidsp.2007.68.75

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Keywords

  • Bcl-2 family
  • bioinformatics
  • structure
  • apoptosis