Next Article in Journal
Diversity of Nonribosomal Peptide Synthetases Involved in the Biosynthesis of Lipopeptide Biosurfactants
Next Article in Special Issue
Comparison of Free Energy Surfaces Calculations from Ab Initio Molecular Dynamic Simulations at the Example of Two Transition Metal Catalyzed Reactions
Previous Article in Journal
Behavioral Impairment and Oxidative Damage Induced by Chronic Application of Nonylphenol
Int. J. Mol. Sci. 2011, 12(1), 128-140; doi:10.3390/ijms12010128
Article

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

1
,
2
,
1
,
3
,
1
,
1
 and
4,*
Received: 26 November 2010 / Revised: 8 December 2010 / Accepted: 23 December 2010 / Published: 30 December 2010
(This article belongs to the Special Issue Applications of Molecular Dynamics)
View Full-Text   |   Download PDF [3698 KB, uploaded 19 June 2014]   |   Browse Figures

Abstract

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.
Keywords: p53; molecular dynamics; S100B; protein interactions p53; molecular dynamics; S100B; protein interactions
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

Pirolli, D.; Carelli Alinovi, C.; Capoluongo, E.; Satta, M.A.; Concolino, P.; Giardina, B.; De Rosa, M.C. Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations. Int. J. Mol. Sci. 2011, 12, 128-140.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert