2PCX

Crystal structure of p53DBD(R282Q) at 1.54-angstrom Resolution

Summary for 2PCX

• Entry DOI: 10.2210/pdb2pcx/pdb
• Related: 1TSR 1UOL 2AC0 2ADY 2AHI 2ATA
• Descriptor: Cellular tumor antigen p53, ZINC ION (3 entities in total)
• Functional Keywords: p53, p53 hotspots, p53 dna-binding domain, p53dbd, p53dbd(r282q), transcription
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 1
• Total formula weight: 24871.61

Authors

Tu, C.,Shaw, G.,Ji, X. (deposition date: 2007-03-30, release date: 2008-04-08, Last modification date: 2023-08-30)

Primary citation

Tu, C.,Tan, Y.H.,Shaw, G.,Zhou, Z.,Bai, Y.,Luo, R.,Ji, X.
Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 angstroms resolution.
Acta Crystallogr.,Sect.D, 64:471-477, 2008

PubMed Abstract: Tumor suppressor p53 is a sequence-specific DNA-binding protein and its central DNA-binding domain (DBD) harbors six hotspots (Arg175, Gly245, Arg248, Arg249, Arg273 and Arg282) for human cancers. Here, the crystal structure of a low-frequency hotspot mutant, p53DBD(R282Q), is reported at 1.54 angstroms resolution together with the results of molecular-dynamics simulations on the basis of the structure. In addition to eliminating a salt bridge, the R282Q mutation has a significant impact on the properties of two DNA-binding loops (L1 and L3). The L1 loop is flexible in the wild type, but it is not flexible in the mutant. The L3 loop of the wild type is not flexible, whereas it assumes two conformations in the mutant. Molecular-dynamics simulations indicated that both conformations of the L3 loop are accessible under biological conditions. It is predicted that the elimination of the salt bridge and the inversion of the flexibility of L1 and L3 are directly or indirectly responsible for deactivating the tumor suppressor p53.

PubMed: 18453682
DOI: 10.1107/S0907444908003338

Experimental method

X-RAY DIFFRACTION (1.54 Å)