3V3B
Structure of the Stapled p53 Peptide Bound to Mdm2
Summary for 3V3B
| Entry DOI | 10.2210/pdb3v3b/pdb |
| Related | 1YCR |
| Related PRD ID | PRD_000857 |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, SAH-p53-8 stapled-peptide, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | oncoprotein, cell cycle, dna repair, cancer, p53-derived peptide, aliphatic staple, ligase-ligase inhibitor complex, ligase/ligase inhibitor |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus, nucleoplasm: Q00987 |
| Total number of polymer chains | 4 |
| Total formula weight | 25237.15 |
| Authors | Baek, S.,Kutchukian, P.S.,Verdine, G.L.,Huber, R.,Holak, T.A.,Ki Won, L.,Popowicz, G.M. (deposition date: 2011-12-13, release date: 2012-01-18, Last modification date: 2024-10-16) |
| Primary citation | Baek, S.,Kutchukian, P.S.,Verdine, G.L.,Huber, R.,Holak, T.A.,Lee, K.W.,Popowicz, G.M. Structure of the stapled p53 peptide bound to Mdm2. J.Am.Chem.Soc., 134:103-106, 2012 Cited by PubMed Abstract: Mdm2 is a major negative regulator of the tumor suppressor p53 protein, a protein that plays a crucial role in maintaining genome integrity. Inactivation of p53 is the most prevalent defect in human cancers. Inhibitors of the Mdm2-p53 interaction that restore the functional p53 constitute potential nongenotoxic anticancer agents with a novel mode of action. We present here a 2.0 Å resolution structure of the Mdm2 protein with a bound stapled p53 peptide. Such peptides, which are conformationally and proteolytically stabilized with all-hydrocarbon staples, are an emerging class of biologics that are capable of disrupting protein-protein interactions and thus have broad therapeutic potential. The structure represents the first crystal structure of an i, i + 7 stapled peptide bound to its target and reveals that rather than acting solely as a passive conformational brace, a staple can intimately interact with the surface of a protein and augment the binding interface. PubMed: 22148351DOI: 10.1021/ja2090367 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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