2fsz
From Proteopedia
(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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| - | [[Image:2fsz.gif|left|200px]]<br /> | + | [[Image:2fsz.gif|left|200px]]<br /><applet load="2fsz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fsz" size=" | + | |
caption="2fsz, resolution 2.200Å" /> | caption="2fsz, resolution 2.200Å" /> | ||
'''A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta'''<br /> | '''A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Evidence is presented that the estrogen antagonist 4-hydroxytamoxifen (HT) | + | 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== | ==About this Structure== | ||
| - | 2FSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with OHT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2FSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=OHT:'>OHT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FSZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: nuclear hormone binding domain]] | [[Category: nuclear hormone binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:51 2008'' |
Revision as of 15:24, 21 February 2008
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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 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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