3OS9
Estrogen Receptor
Summary for 3OS9
| Entry DOI | 10.2210/pdb3os9/pdb |
| Related | 3OS8 3OSA |
| Descriptor | Estrogen receptor, 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol (3 entities in total) |
| Functional Keywords | estrogen receptor complex, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 120536.76 |
| Authors | Bruning, J.,Parent, A.A.,Gil, G.,Zhao, M.,Nowak, J.,Pace, M.C.,Smith, C.L.,Afonine, P.V.,Adams, P.D.,Katzenellenbogen, J.A.,Nettles, K.W. (deposition date: 2010-09-08, release date: 2010-11-10, Last modification date: 2024-02-21) |
| Primary citation | Bruning, J.B.,Parent, A.A.,Gil, G.,Zhao, M.,Nowak, J.,Pace, M.C.,Smith, C.L.,Afonine, P.V.,Adams, P.D.,Katzenellenbogen, J.A.,Nettles, K.W. Coupling of receptor conformation and ligand orientation determine graded activity. Nat.Chem.Biol., 6:837-843, 2010 Cited by PubMed Abstract: Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity. PubMed: 20924370DOI: 10.1038/nchembio.451 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.303 Å) |
Structure validation
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