Stability and structural recovery of the tetramerization domain of p53-R337H mutant induced by a designed templating ligand.

ABSTRACT: Protein p53 is a transcription factor crucial for cell cycle and genome integrity. It is able to induce both cell arrest when DNA is damaged and the expression of DNA repair machinery. When the damage is irreversible, it triggers apoptosis. Indeed, the protein, which is a homotetramer, is mutated in most human cancers. For instance, the inherited mutation p53-R337H results in destabilization of the tetramer and, consequently, leads to an organism prone to tumor setup. We describe herein a rational designed molecule capable of holding together the four monomers of the mutated p53-R337H protein, recovering the tetramer integrity as in the wild-type structure. Two ligand molecules, based on a conical calix[4]arene with four cationic guanidiniomethyl groups at the wider edge (upper rim) and hy

SUBMITTER: Gordo S 

PROVIDER: S-EPMC2575436 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature