Insight into a novel p53 single point mutation (G389E) by Molecular Dynamics Simulations.

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.

Linkage between I172N mutation, a marker of 21-hydroxylase deficiency, and a single nucleotide polymorphism in Int6 of CYP21B gene: a genetic study of Sardinian family.

Congenital adrenal hyperplasia (CAH) is a genetic disorder due to 21-hydroxylase deficiency. More than 90% of CAH cases are caused by mutations of CYP21B gene, most of which are the result of microconversion events between the functional gene and its pseudogene. Using a combination of RFLP and direct sequencing analysis, in this paper we describe the genetic study of a Sardinian family carrying I172N mutation in linkage with a SNP namely 1636 Int6.