1T4E: Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor

HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.
PDB ID: 1T4EDownload
MMDB ID: 31804
PDB Deposition Date: 2004/4/29
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 1T4E: dimeric; determined by author
Molecular Components in 1T4E
Label Count Molecule
Proteins (2 molecules)
Ubiquitin-protein Ligase E3 Mdm2(Gene symbol: MDM2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB