Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations

Ettore Domenico Capoluongo, Davide Pirolli, Cristiana Carelli Alinovi, Maria Antonia Satta, Paola Concolino, Bruno Giardina, Maria Cristina De Rosa

Research output: Contribution to journalArticle


The majority of inactivating mutations of p53 reside in the central core DNA binding domain of the protein. In this computational study, we investigated the structural effects of a novel p53 mutation (G389E), identified in a patient with congenital adrenal hyperplasia, which is located within the extreme C-terminal domain (CTD) of p53, an unstructured, flexible region (residues 367-393) of major importance for the regulation of the protein. Based on the three-dimensional structure of a carboxyl-terminal peptide of p53 in complex with the S100B protein, which is involved in regulation of the tumor suppressor activity, a model of wild type (WT) and mutant extreme CTD was developed by molecular modeling and molecular dynamics simulation. It was found that the G389E amino acid replacement has negligible effects on free p53 in solution whereas it significantly affects the interactions of p53 with the S100B protein. The results suggest that the observed mutation may interfere with p53 transcription activation and provide useful information for site-directed mutagenesis experiments.
Original languageEnglish
Pages (from-to)128-140
Number of pages13
JournalInternational Journal of Molecular Sciences
Publication statusPublished - 2010




Dive into the research topics of 'Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations'. Together they form a unique fingerprint.

Cite this