4IUI
Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with Dynamic WAY derivative, 4a
Summary for 4IUI
| Entry DOI | 10.2210/pdb4iui/pdb |
| Related | 4IU7 4IV2 4IV4 4IVW 4IVY 4IW6 4IW8 4IWC 4IWF |
| Descriptor | Estrogen receptor, Nuclear receptor coactivator 2, 4-[1-butyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol, ... (4 entities in total) |
| Functional Keywords | nuclear hormone receptor, transcription factor, ligand binding, nucleus, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 59632.19 |
| Authors | Nwachukwu, J.C.,Srinivasan, S.,Parent, A.A.,Cavett, V.,Nowak, J.,Hughes, T.S.,Kojetin, D.J.,Katzenellenbogen, J.A.,Nettles, K.W. (deposition date: 2013-01-21, release date: 2013-03-27, Last modification date: 2023-09-20) |
| Primary citation | Srinivasan, S.,Nwachukwu, J.C.,Parent, A.A.,Cavett, V.,Nowak, J.,Hughes, T.S.,Kojetin, D.J.,Katzenellenbogen, J.A.,Nettles, K.W. Ligand binding dynamics rewire cellular signaling via Estrogen Receptor-alpha Nat.Chem.Biol., 9:326-332, 2013 Cited by PubMed Abstract: Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. Here, we compare a set of ER ligands having dynamic binding orientation (dynamic ligands) with a control set of isomers that are constrained to bind in a single orientation (constrained ligands). Proliferation of breast cancer cells directed by constrained ligands is associated with DNA binding, coactivator recruitment and activation of the estrogen-induced gene GREB1, reflecting a highly interconnected signaling network. In contrast, proliferation driven by dynamic ligands is associated with induction of ERα-mediated transcription in a DNA-binding domain (DBD)-dependent manner. Further, dynamic ligands showed enhanced anti-inflammatory activity. The DBD-dependent profile was predictive of these signaling patterns in a larger diverse set of natural and synthetic ligands. Thus, ligand dynamics directs unique signaling pathways and reveals a new role of the DBD in allosteric control of ERα-mediated signaling. PubMed: 23524984DOI: 10.1038/nchembio.1214 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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