2fsz
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(New page: 200px<br /> <applet load="2fsz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fsz, resolution 2.200Å" /> '''A second binding s...)
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Revision as of 20:03, 12 November 2007
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A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta
Overview
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.
About this Structure
2FSZ is a Single protein structure of sequence from Homo sapiens with OHT as ligand. Full crystallographic information is available from OCA.
Reference
A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta., Wang Y, Chirgadze NY, Briggs SL, Khan S, Jensen EV, Burris TP, Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9908-11. Epub 2006 Jun 16. PMID:16782818
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