4XI3
Estrogen Receptor Alpha Ligand Binding Domain in Complex with Bazedoxifene
Summary for 4XI3
| Entry DOI | 10.2210/pdb4xi3/pdb |
| Descriptor | Estrogen receptor, Bazedoxifene (3 entities in total) |
| Functional Keywords | estrogen receptor, serm, bazedoxifene, breast cancer, nuclear hormone receptor, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 112960.98 |
| Authors | Fanning, S.W.,Mayne, C.G.,Toy, W.,Carlson, K.,Greene, B.,Nowak, J.,Walter, R.,Panchamukhi, S.,Tajhorshid, E.,Nettles, K.W.,Chandarlapaty, S.,Katzenellenbogen, J.,Greene, G.L. (deposition date: 2015-01-06, release date: 2016-01-13, Last modification date: 2024-03-06) |
| Primary citation | Fanning, S.W.,Jeselsohn, R.,Dharmarajan, V.,Mayne, C.G.,Karimi, M.,Buchwalter, G.,Houtman, R.,Toy, W.,Fowler, C.E.,Han, R.,Laine, M.,Carlson, K.E.,Martin, T.A.,Nowak, J.,Nwachukwu, J.C.,Hosfield, D.J.,Chandarlapaty, S.,Tajkhorshid, E.,Nettles, K.W.,Griffin, P.R.,Shen, Y.,Katzenellenbogen, J.A.,Brown, M.,Greene, G.L. The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells. Elife, 7:-, 2018 Cited by PubMed Abstract: Acquired resistance to endocrine therapy remains a significant clinical burden for breast cancer patients. Somatic mutations in the (estrogen receptor alpha (ERα)) gene ligand-binding domain (LBD) represent a recognized mechanism of acquired resistance. Antiestrogens with improved efficacy versus tamoxifen might overcome the resistant phenotype in ER +breast cancers. Bazedoxifene (BZA) is a potent antiestrogen that is clinically approved for use in hormone replacement therapies. We found that BZA possesses improved inhibitory potency against the Y537S and D538G ERα mutants compared to tamoxifen and has additional inhibitory activity in combination with the CDK4/6 inhibitor palbociclib. In addition, comprehensive biophysical and structural biology studies show BZA's selective estrogen receptor degrading (SERD) properties that override the stabilizing effects of the Y537S and D538G ERα mutations. PubMed: 30489256DOI: 10.7554/eLife.37161 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.491 Å) |
Structure validation
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