2FSZ

A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta

Summary for 2FSZ

• Entry DOI: 10.2210/pdb2fsz/pdb
• Descriptor: Estrogen receptor beta, 4-HYDROXYTAMOXIFEN (3 entities in total)
• Functional Keywords: nuclear hormone binding domain, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q92731
• Total number of polymer chains: 2
• Total formula weight: 57037.61

Authors

Wang, Y. (deposition date: 2006-01-23, release date: 2006-07-11, Last modification date: 2024-02-14)

Primary citation

Wang, Y.,Chirgadze, N.Y.,Briggs, S.L.,Khan, S.,Jensen, E.V.,Burris, T.P.
A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta
Proc.Natl.Acad.Sci.Usa, 103:9908-9911, 2006

PubMed Abstract: Evidence is presented that the estrogen antagonist 4-hydroxytamoxifen (HT) can occupy not only the core binding pocket within the ligand-binding domain of estrogen receptor (ER) beta but also a second site on its surface. The crystal structure of the ligand-binding domain (LBD) associated with HT was determined to 2.2 A and revealed two molecules of HT bound to the protein. One was located in the consensus ligand-binding pocket, whereas the other bound to a site that overlaps with the hydrophobic groove of the coactivator recognition surface. Relative to the ERalpha-tamoxifen structure, helix 12 has been displaced from the coactivator recognition surface and occupies a unique position. Although it has been demonstrated that association of the antagonist with the core ligand-binding pocket is sufficient to induce an antagonist ligand-binding domain conformation, this structure suggests that small molecules may directly antagonize receptor-coactivator interactions. These results provide a direct demonstration of two binding sites for HT in ERbeta, as has been previously suggested for ERalpha by using biochemical methods, and represent a crystal structure of a small nonpeptide molecule occupying the coactivator recognition site.

PubMed: 16782818
DOI: 10.1073/pnas.0510596103

Experimental method

X-RAY DIFFRACTION (2.2 Å)