7ygi

Crystal structure of p53 DBD domain in complex with azurin

spinqualitylabelsall models 7ygi, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ygi is a 4 chain structure with sequence from Homo sapiens and Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: K, NA, PO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Structural basis of bacterial effector protein azurin targeting tumor suppressor p53 and inhibiting its ubiquitination.,Hu J, Jiang W, Zuo J, Shi D, Chen X, Yang X, Zhang W, Ma L, Liu Z, Xing Q Commun Biol. 2023 Jan 17;6(1):59. doi: 10.1038/s42003-023-04458-1. PMID:36650277 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also P53 3D structures

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