Structural effects of the L145Q, V157F, and R282W cancer-associated mutations in the p53 DNA-binding core domain.

ABSTRACT: The p53 tumor suppressor is a transcription factor involved in many important signaling pathways, such as apoptosis and cell-cycle arrest. In over half of human cancers, p53 function is compromised by a mutation in its gene. Mutations in the p53 DNA-binding core domain destabilize the structure and reduce DNA-binding activity. We performed molecular dynamics simulations at physiological temperature to study the structural and dynamic effects of the L145Q, V157F, and R282W cancer-associated mutations in comparison to the wild-type protein. While there were common regions of destabilization in the mutant simulations, structural changes particular to individual mutations were also observed. Significant backbone deviations of the H2 helix and S7-S8 loop were observed in all mutant simulations;

SUBMITTER: Calhoun S 

PROVIDER: S-EPMC3117291 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature