1yy4

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[[Image:1yy4.gif|left|200px]]<br /><applet load="1yy4" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1yy4, resolution 2.70&Aring;" />
 
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'''Crystal structure of estrogen receptor beta complexed with 1-chloro-6-(4-hydroxy-phenyl)-naphthalen-2-ol'''<br />
 
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==Overview==
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==Crystal structure of estrogen receptor beta complexed with 1-chloro-6-(4-hydroxy-phenyl)-naphthalen-2-ol==
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The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.
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<StructureSection load='1yy4' size='340' side='right'caption='[[1yy4]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1yy4]] is a 4 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=1YY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YY4 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]] 2.7&#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=4NA:1-CHLORO-6-(4-HYDROXYPHENYL)-2-NAPHTHOL'>4NA</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=1yy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yy4 OCA], [https://pdbe.org/1yy4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yy4 RCSB], [https://www.ebi.ac.uk/pdbsum/1yy4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yy4 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/yy/1yy4_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=1yy4 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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1YY4 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=4NA:'>4NA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YY4 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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ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity., Mewshaw RE, Edsall RJ Jr, Yang C, Manas ES, Xu ZB, Henderson RA, Keith JC Jr, Harris HA, J Med Chem. 2005 Jun 16;48(12):3953-79. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15943471 15943471]
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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: Harris, H A.]]
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[[Category: Edsall Jr RJ]]
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[[Category: Henderson, R A.]]
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[[Category: Harris HA]]
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[[Category: Jr., J C.Keith.]]
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[[Category: Henderson RA]]
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[[Category: Jr., R J.Edsall.]]
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[[Category: Keith Jr JC]]
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[[Category: Manas, E S.]]
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[[Category: Manas ES]]
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[[Category: Mewshaw, R E.]]
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[[Category: Mewshaw RE]]
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[[Category: Xu, Z B.]]
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[[Category: Xu ZB]]
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[[Category: Yang, C.]]
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[[Category: Yang C]]
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[[Category: 4NA]]
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[[Category: agonist]]
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[[Category: er]]
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[[Category: er-beta]]
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[[Category: estrogen]]
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[[Category: estrogen receptor]]
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[[Category: estrogen receptor beta]]
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[[Category: nuclear receptor]]
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[[Category: transcription factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:17 2008''
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Current revision

Crystal structure of estrogen receptor beta complexed with 1-chloro-6-(4-hydroxy-phenyl)-naphthalen-2-ol

PDB ID 1yy4

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