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==Human Estrogen Receptor beta Ligand-binding Domain in Complex with (S)-3-(2-chloro-4-hydroxyphenyl)-2-(4-hydroxyphenyl)propanenitrile==
<StructureSection load='7xwp' size='340' side='right'caption='[[7xwp]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xwp]] 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=7XWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XWP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.919&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I1I:(2~{S})-3-(2-chloranyl-4-oxidanyl-phenyl)-2-(4-hydroxyphenyl)propanenitrile'>I1I</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xwp OCA], [https://pdbe.org/7xwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xwp RCSB], [https://www.ebi.ac.uk/pdbsum/7xwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xwp ProSAT]</span></td></tr>
</table>
== 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.
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== Publication Abstract from PubMed ==
Estrogen receptors (ERs) are ligand-activated transcription factors, with two subtypes ERalpha and ERbeta. The endogenous ligand of ERs is the common 17beta-estradiol, and the ligand-binding pocket of ERalpha and ERbeta is very similar. Nevertheless, some ERbeta-selective agonist ligands have been reported. DPN (diarylpropionitrile) is a widely used ERbeta-selective agonist; however, the structure of the ERbeta-DPN complex has not been solved. Therefore, the bound-state conformation of DPN and its enantioselectivity remain unresolved. In this report, we present the structures of the complexes of ERbeta with DPN or its derivatives that include a chlorine atom by the X-ray crystallography. Additionally, we measured the binding affinity between ERbeta and DPN or derivatives by isothermal titration calorimetry (ITC) and estimated the binding affinity by fragment molecular orbital (FMO) calculations. We also examined the correlation between the ITC data and results from the FMO calculations. FMO calculations showed that S-DPN interacts strongly with three amino acids (Glu305, Phe356, and His475) of ERbeta, and ITC measurements confirmed that the chlorine atom of the DPN derivatives enhances binding affinity. The enthalpy change by ITC correlated strongly with the interaction energy (total IFIEs; inter-fragment interaction energies) calculated by FMO (R = 0.870). We propose that FMO calculations are a valuable approach for enhancing enthalpy contributions in drug design, and its scope of applications includes halogen atoms such as chlorine. This study is the first quantitative comparison of thermodynamic parameters obtained from ITC measurements and FMO calculations, providing new insights for future precise drug design.

Evaluating the correlation of binding affinities between isothermal titration calorimetry and fragment molecular orbital method of estrogen receptor beta with diarylpropionitrile (DPN) or DPN derivatives.,Handa C, Yamazaki Y, Yonekubo S, Furuya N, Momose T, Ozawa T, Furuishi T, Fukuzawa K, Yonemochi E J Steroid Biochem Mol Biol. 2022 Sep;222:106152. doi:, 10.1016/j.jsbmb.2022.106152. Epub 2022 Jul 8. PMID:35810932<ref>PMID:35810932</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xwp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Furuya N]]
[[Category: Handa C]]