Journal article
Common Conformational Effects of p53 Mutations
Journal of protein chemistry, v 20(2), pp 101-105
01 Feb 2001
PMID: 11563689
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The tumor suppressor gene p53 has been identified as the most frequent target of genetic alterations in human cancers. Most of these mutations occur in highly conserved regions in the DNA-binding core domain of the p53 protein, suggesting that the amino acid residues in these regions are critical for maintaining normal p53 structure and function. We previously used molecular dynamics calculations to demonstrate that several amino acid substitutions in these regions that are induced by environmental carcinogens and found in human tumors produce certain common conformational changes in the mutant proteins that differ substantially from the wild-type structure. In order to determine whether these conformational changes are consistent for other p53 mutants, we have now used molecular dynamics to determine the structure of the DNA-binding core domain of seven other environmentally induced, cancer-related p53 mutants, namely His 175, Asp 245, Asn 245, Trp 248, Met 249, Ser 278, and Lys 286. The results indicate that all of these mutants differ substantially from the wild-type structure in certain discrete regions and that some of these conformational changes are similar for these mutants as well as those determined previously. The changes are also consistent with experimental evidence for alterations in structure in p53 mutants determined by epitope detectability using monoclonal antibodies directed against these regions of predicted conformational change.[PUBLICATION ABSTRACT]
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Details
- Title
- Common Conformational Effects of p53 Mutations
- Creators
- J Chen - Telik, Inc.R Rosal - Columbia UniversityS Smith - Veterans Health AdministrationM Pincus - Veterans Health AdministrationP Brandt-rauf - Columbia University
- Publication Details
- Journal of protein chemistry, v 20(2), pp 101-105
- Publisher
- Springer Nature B.V
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000170973000001
- Scopus ID
- 2-s2.0-0034851525
- Other Identifier
- 991019342456004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology