4J3E
The 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3a
Summary for 4J3E
| Entry DOI | 10.2210/pdb4j3e/pdb |
| Related | 1RV1 4IPF |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, 4-({(4S,5R)-4,5-bis(4-chlorophenyl)-2-[4-methoxy-2-(propan-2-yloxy)phenyl]-4,5-dihydro-1H-imidazol-1-yl}carbonyl)piperazin-2-one, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | mdm2, protein-protein interaction, imidazoline, ligase-antagonist complex, e3 ubiquitin ligase, p53, nucleus, ligase/antagonist |
| Biological source | Xenopus laevis (clawed frog,common platanna,platanna) |
| Cellular location | Nucleus, nucleoplasm (By similarity): P56273 |
| Total number of polymer chains | 1 |
| Total formula weight | 10640.17 |
| Authors | Graves, B.J.,Lukacs, C.M.,Kammlott, R.U.,Crowther, R. (deposition date: 2013-02-05, release date: 2013-04-24, Last modification date: 2024-02-28) |
| Primary citation | Vu, B.,Wovkulich, P.,Pizzolato, G.,Lovey, A.,Ding, Q.,Jiang, N.,Liu, J.J.,Zhao, C.,Glenn, K.,Wen, Y.,Tovar, C.,Packman, K.,Vassilev, L.,Graves, B. Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development. ACS Med Chem Lett, 4:466-469, 2013 Cited by PubMed Abstract: The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome. Many tumors produce high levels of MDM2, thereby impairing p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts. PubMed: 24900694DOI: 10.1021/ml4000657 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.91 Å) |
Structure validation
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