1RV1
CRYSTAL STRUCTURE OF HUMAN MDM2 WITH AN IMIDAZOLINE INHIBITOR
Summary for 1RV1
| Entry DOI | 10.2210/pdb1rv1/pdb |
| Related | 1YCR |
| Descriptor | Ubiquitin-protein ligase E3 Mdm2, CIS-[4,5-BIS-(4-BROMOPHENYL)-2-(2-ETHOXY-4-METHOXYPHENYL)-4,5-DIHYDROIMIDAZOL-1-YL]-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]METHANONE (3 entities in total) |
| Functional Keywords | mdm2, p53, protein-protein interaction, ligase |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus, nucleoplasm: Q00987 |
| Total number of polymer chains | 3 |
| Total formula weight | 33614.70 |
| Authors | Lukacs, C.,Kammlott, U.,Graves, B. (deposition date: 2003-12-12, release date: 2004-01-20, Last modification date: 2023-08-23) |
| Primary citation | Vassilev, L.T.,Vu, B.T.,Graves, B.,Carvajal, D.,Podlaski, F.,Filipovic, Z.,Kong, N.,Kammlott, U.,Lukacs, C.,Klein, C.,Fotouhi, N.,Liu, E.A. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303:844-848, 2004 Cited by PubMed Abstract: MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice. PubMed: 14704432DOI: 10.1126/science.1092472 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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