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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 2.200&Aring;" /> '''A second binding s...)
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[[Image:2fsz.gif|left|200px]]<br />
 
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<applet load="2fsz" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2fsz, resolution 2.200&Aring;" />
 
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'''A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta'''<br />
 
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==Overview==
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==A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta==
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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.
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<StructureSection load='2fsz' size='340' side='right'caption='[[2fsz]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fsz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FSZ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OHT:4-HYDROXYTAMOXIFEN'>OHT</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fsz OCA], [https://pdbe.org/2fsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fsz RCSB], [https://www.ebi.ac.uk/pdbsum/2fsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fsz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ESR2_HUMAN ESR2_HUMAN] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fs/2fsz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fsz ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FSZ OCA].
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*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16782818 16782818]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Wang, Yong]]
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[[Category: Wang Y]]
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[[Category: OHT]]
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[[Category: nuclear hormone binding domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:10:10 2007''
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Current revision

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

PDB ID 2fsz

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