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Conformational Effects Of Selected Cancer-Related Amino Acid Substitutions In The p53 Protein
Journal article   Peer reviewed

Conformational Effects Of Selected Cancer-Related Amino Acid Substitutions In The p53 Protein

Paul W. Brandt-Rauf, Immaculata DeVivo, Daryll C. Dykes and Matthew R. Pincus
Journal of biomolecular structure & dynamics, v 10(2)
01 Oct 1992
PMID: 1466808

Abstract

The tumor suppressor gene p53 has been identified as the most frequent target of genetic alterations in human cancers. Cancer-related mutations in the human p53 protein tend to cluster in four of the five highly conserved domains of the protein, and, in particular, in the central region of domain IV from residues 241 to 253. Using conformational energy analysis based on ECEPP (Empirical Conformational Energies for Polypeptides Program), we have determined the preferred three dimensional structures for this tridecapeptide sequence for the human wild-type p53 protein and four cancer-related mutant p53 proteins (Ala 245, Ile 246, Trp 248, Ser249). The results show that the mutant peptides adopt conformations that are distinctly different from that of the wild-type peptide. These results are consistent with experimental conformational studies demonstrating altered detectability of antigenic epitopes in murine wild-type and mutant p53 proteins. These results suggest that the oncogenic effects of human mutant p53 proteins may be mediated by distinct local conformational changes in the protein.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Biophysics
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