View source for 1u3r

==Crystal Structure of Estrogen Receptor beta complexed with WAY-338==
<StructureSection load='1u3r' size='340' side='right' caption='[[1u3r]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1u3r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U3R FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=338:2-(5-HYDROXY-NAPHTHALEN-1-YL)-1,3-BENZOOXAZOL-6-OL'>338</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u3q|1u3q]], [[1u3s|1u3s]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESR2, NR3A2, ESTRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u3r OCA], [http://pdbe.org/1u3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u3r RCSB], [http://www.ebi.ac.uk/pdbsum/1u3r PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u3r_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are &gt;100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --&gt; ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being &gt;200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least approximately 50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.

Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands.,Malamas MS, Manas ES, McDevitt RE, Gunawan I, Xu ZB, Collini MD, Miller CP, Dinh T, Henderson RA, Keith JC Jr, Harris HA J Med Chem. 2004 Oct 7;47(21):5021-40. PMID:15456246<ref>PMID:15456246</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1u3r" style="background-color:#fffaf0;"></div>

==See Also==
*[[Estrogen receptor|Estrogen receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Collini, M D]]
[[Category: Dinh, T]]
[[Category: Gunawan, I]]
[[Category: Harris, H A]]
[[Category: Henderson, R A]]
[[Category: Keith, J C]]
[[Category: Malamas, M S]]
[[Category: Manas, E S]]
[[Category: McDevitt, R E]]
[[Category: Miller, C P]]
[[Category: Xu, Z B]]
[[Category: Agonist]]
[[Category: Er]]
[[Category: Er-beta]]
[[Category: Estrogen]]
[[Category: Estrogen receptor]]
[[Category: Estrogen receptor beta]]
[[Category: Nuclear receptor]]
[[Category: Transcription]]
[[Category: Transcription factor]]