ArticleBiochemistry2011
Structural effects of the L145Q, V157F, and R282W cancer-associated mutations in the p53 DNA-binding core domain.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Article
- Covalent drug rescue of multiple p53 mutants by stabilizing vinyl sulfone fragments hints to a specific refolding mechanism for R282W.Protein science : a publication of the Protein Society · 2026Article
- Distinct Associations ofGenes · 2026Article
- Review
- OPUS-Mut: Studying the Effect of Protein Mutation through Side-Chain Modeling.Journal of chemical theory and computation · 2023Article
- Clinical applications of liquid biopsy in HPV-negative and HPV-positive head and neck squamous cell carcinoma: advances and challenges.Exploration of targeted anti-tumor therapy · 2022Review
- Mutations ofJournal of veterinary research · 2021Article
- Structural and Drug Targeting Insights on Mutant p53.Cancers · 2021Review
- Ring finger 20/ring finger 40/WW domain-containing adaptor with coiled-coil complex interacts with p53 to regulate gene transcription in DNA damage response.Oncology letters · 2021Article
- Investigating Conformational Dynamics and Allostery in the p53 DNA-Binding Domain Using Molecular Simulations.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Cervical carcinomas with serous-like papillary and micropapillary components: illustrating the heterogeneity of primary cervical carcinomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Article
- Tumorigenic p53 mutants undergo common structural disruptions including conversion to α-sheet structure.Protein science : a publication of the Protein Society · 2020Article
- Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting.Journal of molecular cell biology · 2019Review
- T-cell large granular lymphocyte leukemia transfomation into aggressive T-cell lymphoma: a report of two cases with molecular characterization.Haematologica · 2019Article
- Lung-Enriched Mutations in the p53 Tumor Suppressor: A Paradigm for Tissue-Specific Gain of Oncogenic Function.Molecular cancer research : MCR · 2019Review
- Enhanced breast cancer progression by mutant p53 is inhibited by the circular RNA circ-Ccnb1.Cell death and differentiation · 2018Article
- "Infostery" analysis of short molecular dynamics simulations identifies highly sensitive residues and predicts deleterious mutations.Scientific reports · 2018Article
- Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.PloS one · 2017Article
- Mutational analysis of TP53 gene in Tunisian familial hematological malignancies and sporadic acute leukemia cases.Familial cancer · 2017Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The p53 tumor suppressor is a transcription factor involved in many important signaling pathways, such as apoptosis and cell-cycle arrest. In over half of human cancers, p53 function is compromised by a mutation in its gene. Mutations in the p53 DNA-binding core domain destabilize the structure and reduce DNA-binding activity. We performed molecular dynamics simulations at physiological temperature to study the structural and dynamic effects of the L145Q, V157F, and R282W cancer-associated mutations in comparison to the wild-type protein. While there were common regions of destabilization in the mutant simulations, structural changes particular to individual mutations were also observed. Significant backbone deviations of the H2 helix and S7-S8 loop were observed in all mutant simulations; the H2 helix binds to DNA. In addition, the L145Q and V157F mutations, which are located in the β-sandwich core of the domain, disrupted the β-sheet structure and the loop-sheet-helix motif. The R282W mutation caused distortion of the loop-sheet-helix motif, but otherwise this mutant was similar to the wild-type structure. The introduction of these mutations caused rearrangement of the DNA-binding surface, consistent with their reduced DNA-binding activity. The simulations reveal detailed effects of the mutations on the stability and dynamics of p53 that may provide insight for therapeutic approaches.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.