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

Davide Pirolli 1 email, Cristiana Carelli Alinovi 2 email, Ettore Capoluongo 1 email, Maria Antonia Satta 3 email, Paola Concolino 1 email, Bruno Giardina 1 email and Maria Cristina De Rosa 4,* email
1 Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy 2 Dipartimento di Scienze Motorie e della Salute, Università di Cassino, Via S. Angelo-Località Folcara, 03043 Cassino (FR), Italy 3 Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy 4 Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Largo F. Vito 1, 00168 Rome, Italy
* Author to whom correspondence should be addressed.
Received: 26 November 2010; in revised form: 8 December 2010 / Accepted: 23 December 2010 / Published: 30 December 2010
(This article belongs to the Special Issue Applications of Molecular Dynamics)
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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

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Cite This Article

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.

AMA Style

Pirolli D, Carelli Alinovi C, Capoluongo E, Satta MA, Concolino P, Giardina B, De Rosa MC. Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2011; 12(1):128-140.

Chicago/Turabian Style

Pirolli, Davide; Carelli Alinovi, Cristiana; Capoluongo, Ettore; Satta, Maria Antonia; Concolino, Paola; Giardina, Bruno; De Rosa, Maria Cristina. 2011. "Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations." Int. J. Mol. Sci. 12, no. 1: 128-140.

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