PDB 4HFZ deposited: 2012-10-05 modified: 2013-08-21
Title Crystal Structure of an MDM2/P53 Peptide Complex
Authors Anil, B., Endicott, J.A., Noble, M.E., Riedinger, C.
Structure factors resolution 2.694 rfactor 0.19527 rfree 0.24679
DPI 1.05 theoretical min: 0.42
Related PDB Entries 4HG7

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.

Acta Crystallogr.,Sect.D 2013 Aug; 69(Pt 8):1358-1366 doi:10.1107/S0907444913004459

Cross References
Database source Identifier Description
PubMed 23897459 ABCRE6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4HFZ/1 4HFZ 1 dimer 0 2 1 780
4HFZ/2 4HFZ 2 dimer 0 2 0 828