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 ex...
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| Format: | Article |
| Language: | English |
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MDPI AG
2010-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/12/1/128/ |
| _version_ | 1811251624345075712 |
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| author | Maria Cristina De Rosa Bruno Giardina Paola Concolino Cristiana Carelli Alinovi Maria Antonia Satta Ettore Capoluongo Davide Pirolli |
| author_facet | Maria Cristina De Rosa Bruno Giardina Paola Concolino Cristiana Carelli Alinovi Maria Antonia Satta Ettore Capoluongo Davide Pirolli |
| author_sort | Maria Cristina De Rosa |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-d0a09d4e2ae24a959ca3bbeb372a4bf4 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T16:23:12Z |
| publishDate | 2010-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d0a09d4e2ae24a959ca3bbeb372a4bf42022-12-22T03:25:29ZengMDPI AGInternational Journal of Molecular Sciences1422-00672010-12-0112112814010.3390/ijms12010128Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics SimulationsMaria Cristina De RosaBruno GiardinaPaola ConcolinoCristiana Carelli AlinoviMaria Antonia SattaEttore CapoluongoDavide PirolliThe 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.http://www.mdpi.com/1422-0067/12/1/128/p53molecular dynamicsS100Bprotein interactions |
| spellingShingle | Maria Cristina De Rosa Bruno Giardina Paola Concolino Cristiana Carelli Alinovi Maria Antonia Satta Ettore Capoluongo Davide Pirolli Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations International Journal of Molecular Sciences p53 molecular dynamics S100B protein interactions |
| title | Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations |
| title_full | Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations |
| title_fullStr | Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations |
| title_full_unstemmed | Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations |
| title_short | Insight into a Novel p53 Single Point Mutation (G389E) by Molecular Dynamics Simulations |
| title_sort | insight into a novel p53 single point mutation g389e by molecular dynamics simulations |
| topic | p53 molecular dynamics S100B protein interactions |
| url | http://www.mdpi.com/1422-0067/12/1/128/ |
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