4J8N
Aurora A Kinase Apo
Summary for 4J8N
| Entry DOI | 10.2210/pdb4j8n/pdb |
| Related | 4J8M |
| Descriptor | Aurora kinase A (2 entities in total) |
| Functional Keywords | aurora a, kinase domain, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : O14965 |
| Total number of polymer chains | 4 |
| Total formula weight | 129436.49 |
| Authors | Meyerowitz, J.G.,Gustafson, W.C.,Shokat, K.M.,Weiss, W.A. (deposition date: 2013-02-14, release date: 2014-09-10, Last modification date: 2024-02-28) |
| Primary citation | Gustafson, W.C.,Meyerowitz, J.G.,Nekritz, E.A.,Chen, J.,Benes, C.,Charron, E.,Simonds, E.F.,Seeger, R.,Matthay, K.K.,Hertz, N.T.,Eilers, M.,Shokat, K.M.,Weiss, W.A. Drugging MYCN through an Allosteric Transition in Aurora Kinase A. Cancer Cell, 26:414-427, 2014 Cited by PubMed Abstract: MYC proteins are major drivers of cancer yet are considered undruggable because their DNA binding domains are composed of two extended alpha helices with no apparent surfaces for small-molecule binding. Proteolytic degradation of MYCN protein is regulated in part by a kinase-independent function of Aurora A. We describe a class of inhibitors that disrupts the native conformation of Aurora A and drives the degradation of MYCN protein across MYCN-driven cancers. Comparison of cocrystal structures with structure-activity relationships across multiple inhibitors and chemotypes, coupled with mechanistic studies and biochemical assays, delineates an Aurora A conformation-specific effect on proteolytic degradation of MYCN, rather than simple nanomolar-level inhibition of Aurora A kinase activity. PubMed: 25175806DOI: 10.1016/j.ccr.2014.07.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.135 Å) |
Structure validation
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