2OUZ
Crystal Structure of Estrogen Receptor alpha-lasofoxifene complex
Summary for 2OUZ
| Entry DOI | 10.2210/pdb2ouz/pdb |
| Related | 1ERE 1ERR |
| Descriptor | Estrogen receptor, (5R,6S)-6-PHENYL-5-[4-(2-PYRROLIDIN-1-YLETHOXY)PHENYL]-5,6,7,8-TETRAHYDRONAPHTHALEN-2-OL (3 entities in total) |
| Functional Keywords | nuclear receptor, serm, estrogen, hormone-growth factor complex, hormone/growth factor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29302.57 |
| Authors | Vajdos, F.F.,Pandit, J. (deposition date: 2007-02-12, release date: 2007-05-08, Last modification date: 2023-08-30) |
| Primary citation | Vajdos, F.F.,Hoth, L.R.,Geoghegan, K.F.,Simons, S.P.,LeMotte, P.K.,Danley, D.E.,Ammirati, M.J.,Pandit, J. The 2.0 A crystal structure of the ER{alpha} ligand-binding domain complexed with lasofoxifene Protein Sci., 16:897-905, 2007 Cited by PubMed Abstract: Lasofoxifene is a new and potent selective estrogen receptor modulator (SERM). The structural basis of its interaction with the estrogen receptor has been investigated by crystallographic analysis of its complex with the ligand-binding domain of estrogen receptor alpha at a resolution of 2.0 A. As with other SERMs, lasofoxifene diverts the receptor from its agonist-bound conformation by displacing the C-terminal AF-2 helix into the site at which the LXXLL motif of coactivator proteins would otherwise be able to bind. Lasofoxifene achieves this effect by occupying the space normally filled by residue Leu 540, as well as by modulating the conformation of residues of helix 11 (His 524, Leu 525). A well-defined salt bridge between lasofoxifene and Asp 351 suggests that charge neutralization in this region of the receptor may explain the some of the antiestrogenic effects of lasofoxifene. The results suggest general features of ERalpha/SERM recognition, and add a new dimension to efforts to rationalize differences between the biological activity profiles exhibited by these important pharmacological agents. PubMed: 17456742DOI: 10.1110/ps.062729207 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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