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[[Image:1u3r.gif|left|200px]]


{{Structure
==Crystal Structure of Estrogen Receptor beta complexed with WAY-338==
|PDB= 1u3r |SIZE=350|CAPTION= <scene name='initialview01'>1u3r</scene>, resolution 2.21&Aring;
<StructureSection load='1u3r' size='340' side='right'caption='[[1u3r]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=338:2-(5-HYDROXY-NAPHTHALEN-1-YL)-1,3-BENZOOXAZOL-6-OL'>338</scene>
<table><tr><td colspan='2'>[[1u3r]] 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=1U3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U3R FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21&#8491;</td></tr>
|GENE= ESR2, NR3A2, ESTRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=338:2-(5-HYDROXY-NAPHTHALEN-1-YL)-1,3-BENZOOXAZOL-6-OL'>338</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u3r OCA], [https://pdbe.org/1u3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u3r RCSB], [https://www.ebi.ac.uk/pdbsum/1u3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u3r ProSAT]</span></td></tr>
|RELATEDENTRY=[[1u3q|1U3Q]], [[1u3s|1U3S]]
</table>
|RESOURCES=<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://www.ebi.ac.uk/pdbsum/1u3r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u3r RCSB]</span>
== Function ==
}}
[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.
== 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/main_output.php?pdb_ID=1u3r ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of Estrogen Receptor beta complexed with WAY-338'''
==See Also==
 
*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
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.
 
==About this Structure==
1U3R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3R OCA].
 
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/15456246 15456246]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Collini, M D.]]
[[Category: Collini MD]]
[[Category: Dinh, T.]]
[[Category: Dinh T]]
[[Category: Gunawan, I.]]
[[Category: Gunawan I]]
[[Category: Harris, H A.]]
[[Category: Harris HA]]
[[Category: Henderson, R A.]]
[[Category: Henderson RA]]
[[Category: Jr., J C.Keith.]]
[[Category: Keith Jr JC]]
[[Category: Malamas, M S.]]
[[Category: Malamas MS]]
[[Category: Manas, E S.]]
[[Category: Manas ES]]
[[Category: McDevitt, R E.]]
[[Category: McDevitt RE]]
[[Category: Miller, C P.]]
[[Category: Miller CP]]
[[Category: Xu, Z B.]]
[[Category: Xu ZB]]
[[Category: agonist]]
[[Category: er]]
[[Category: er-beta]]
[[Category: estrogen]]
[[Category: estrogen receptor]]
[[Category: estrogen receptor beta]]
[[Category: nuclear receptor]]
[[Category: transcription factor]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:05:02 2008''

Latest revision as of 11:43, 14 February 2024

Crystal Structure of Estrogen Receptor beta complexed with WAY-338Crystal Structure of Estrogen Receptor beta complexed with WAY-338

Structural highlights

1u3r is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.21Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1u3r, resolution 2.21Å

Drag the structure with the mouse to rotate

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OCA
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