7YGI
Crystal structure of p53 DBD domain in complex with azurin
Summary for 7YGI
| Entry DOI | 10.2210/pdb7ygi/pdb |
| Descriptor | Cellular tumor antigen p53, Azurin, SODIUM ION, ... (7 entities in total) |
| Functional Keywords | transient complex, tumour suppressor, antitumor protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 71672.80 |
| Authors | Jiang, W.X.,Zuo, J.Q.,Hu, J.J.,Chen, X.Q.,Ma, L.X.,Liu, Z.,Xing, Q. (deposition date: 2022-07-11, release date: 2023-02-08, Last modification date: 2024-10-09) |
| Primary citation | Hu, J.,Jiang, W.,Zuo, J.,Shi, D.,Chen, X.,Yang, X.,Zhang, W.,Ma, L.,Liu, Z.,Xing, Q. Structural basis of bacterial effector protein azurin targeting tumor suppressor p53 and inhibiting its ubiquitination. Commun Biol, 6:59-59, 2023 Cited by PubMed Abstract: Tumor suppressor p53 prevents tumorigenesis by promoting cell cycle arrest and apoptosis through transcriptional regulation. Dysfunction of p53 occurs frequently in human cancers. Thus, p53 becomes one of the most promising targets for anticancer treatment. A bacterial effector protein azurin triggers tumor suppression by stabilizing p53 and elevating its basal level. However, the structural and mechanistic basis of azurin-mediated tumor suppression remains elusive. Here we report the atomic details of azurin-mediated p53 stabilization by combining X-ray crystallography with nuclear magnetic resonance. Structural and mutagenic analysis reveals that the p28 region of azurin, which corresponds to a therapeutic peptide, significantly contributes to p53 binding. This binding stabilizes p53 by disrupting COP1-mediated p53 ubiquitination and degradation. Using the structure-based design, we obtain several affinity-enhancing mutants that enable amplifying the effect of azurin-induced apoptosis. Our findings highlight how the structure of the azurin-p53 complex can be leveraged to design azurin derivatives for cancer therapy. PubMed: 36650277DOI: 10.1038/s42003-023-04458-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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