4HFZ
Crystal Structure of an MDM2/P53 Peptide Complex
Summary for 4HFZ
| Entry DOI | 10.2210/pdb4hfz/pdb |
| Related | 4HG7 |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, Cellular tumor antigen p53, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | mdm2, p53, surface entropy reduction, mutant validation, ligase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus, nucleoplasm: Q00987 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 | 4 |
| Total formula weight | 28550.43 |
| Authors | Anil, B.,Riedinger, C.,Endicott, J.A.,Noble, M.E.M. (deposition date: 2012-10-05, release date: 2013-07-31, Last modification date: 2024-02-28) |
| Primary citation | Anil, B.,Riedinger, C.,Endicott, J.A.,Noble, M.E. The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant. Acta Crystallogr.,Sect.D, 69:1358-1366, 2013 Cited by PubMed Abstract: The p53-binding site of MDM2 holds great promise as a target for therapeutic intervention in MDM2-amplified p53 wild-type forms of cancer. Despite the extensive validation of this strategy, there are relatively few crystallographically determined co-complex structures for small-molecular inhibitors of the MDM2-p53 interaction available in the PDB. Here, a surface-entropy reduction mutant of the N-terminal domain of MDM2 that has been designed to enhance crystallogenesis is presented. This mutant has been validated by comparative ligand-binding studies using differential scanning fluorimetry and fluorescence polarization anisotropy and by cocrystallization with a peptide derived from p53. Using this mutant, the cocrystal structure of MDM2 with the benchmark inhibitor Nutlin-3a has been determined, revealing subtle differences from the previously described co-complex of MDM2 with Nutlin-2. PubMed: 23897459DOI: 10.1107/S0907444913004459 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.694 Å) |
Structure validation
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