Deleterious missense single nucleotide polymorphism alters the structural conformation of human anti-apoptotic Bcl-2 protein

摘要

Identification and understanding the mechanism behind tumorigenesis is crucial for developing new strategies in cancer treatments. In this in silico study, we used the 14 different tools to evaluate the convergent deleterious missense Bcl-2 SNPs. Out of 37 missense single nucleotide polymorphism (SNPs), five are deleterious. Molecular modelling and structural and functional evaluation of the mutant proteins were carried out to understand their clinical significance. All deleterious missense SNPs alter the structural stability of the protein. Also H94P deleterious missense SNPs alter the ligand-binding ability of Bcl-2. The results indicate that the mutant antiapoptotic Bcl-2 protein may contribute to tumorigenesis in different ways, depending upon the mutation location.