2BIM
human p53 core domain mutant M133L-V203A-N239Y-N268D-R273H
Summary for 2BIM
| Entry DOI | 10.2210/pdb2bim/pdb |
| Related | 1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAG 1SAH 1SAI 1SAJ 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YCQ 1YCR 1YCS 2BIN 2BIO 2BIP 2BIQ 3SAK |
| Descriptor | CELLULAR TUMOR ANTIGEN P53, ZINC ION, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | activator, anti-oncogene, apoptosis, disease mutation, dna-binding, dna-binding protein, li-fraumeni syndrome, nuclear protein, p53 dna-binding domain, phosphorylation, polymorphism, second-site suppressor mutation, superstable mutant, transcription regulation, tumor suppressor, transferase, dna binding protein |
| 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 | 2 |
| Total formula weight | 49466.53 |
| Authors | Joerger, A.C.,Fersht, A.R. (deposition date: 2005-01-25, release date: 2005-01-26, Last modification date: 2023-12-13) |
| Primary citation | Joerger, A.C.,Ang, H.C.,Veprintsev, D.B.,Blair, C.M.,Fersht, A.R. Structures of P53 Cancer Mutants and Mechanism of Rescue by Second-Site Suppressor Mutations J.Biol.Chem., 280:16030-, 2005 Cited by PubMed Abstract: We have solved the crystal structures of three oncogenic mutants of the core domain of the human tumor suppressor p53. The mutations were introduced into a stabilized variant. The cancer hot spot mutation R273H simply removes an arginine involved in DNA binding without causing structural distortions in neighboring residues. In contrast, the "structural" oncogenic mutations H168R and R249S induce substantial structural perturbation around the mutation site in the L2 and L3 loops, respectively. H168R is a specific intragenic suppressor mutation for R249S. When both cancer mutations are combined in the same molecule, Arg(168) mimics the role of Arg(249) in wild type, and the wild type conformation is largely restored in both loops. Our structural and biophysical data provide compelling evidence for the mechanism of rescue of mutant p53 by intragenic suppressor mutations and reveal features by which proteins can adapt to deleterious mutations. PubMed: 15703170DOI: 10.1074/JBC.M500179200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
Download full validation report
