View source for 6i61


==Crystal structure of human ERRg LBD in complex with bisphenol-B==
<StructureSection load='6i61' size='340' side='right'caption='[[6i61]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6i61]] is a 1 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=6I61 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I61 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H3W:bisphenol-B'>H3W</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=6i61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i61 OCA], [https://pdbe.org/6i61 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i61 RCSB], [https://www.ebi.ac.uk/pdbsum/6i61 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i61 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ERR3_HUMAN ERR3_HUMAN] Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).<ref>PMID:19067653</ref> <ref>PMID:18063693</ref> <ref>PMID:11864604</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The estrogen-related receptor gamma (ERRgamma, NR3B3) is a constitutively active nuclear receptor which has been proposed to act as a mediator of the low-dose effects of a number of environmental endocrine-disrupting chemicals (EDCs) such as the xenoestrogen bisphenol-A (BPA). To better characterize the ability of exogenous compounds to bind and activate ERRgamma, we used a combination of cell-based, biochemical, structural and computational approaches. A purposely created stable cell line allowed for the determination of the EC50s for over 30 environmental ERRgamma ligands, including previously unknown ones. Interestingly, affinity constants (Kds) of the most potent compounds measured by isothermal titration calorimetry were in the 50-500 nM range, in agreement with their receptor activation potencies. Crystallographic analysis of the interaction between the ERRgamma ligand-binding domain (LBD) and compounds of the bisphenol, alkylphenol and naphthol families revealed a partially shared binding mode and minimal alterations of the receptor conformation upon ligand binding. Further biophysical characterizations coupled to molecular dynamics simulations suggested a mechanism through which ERRgamma ligands would exhibit their agonistic properties by preserving the transcriptionally active form of the receptor while rigidifying some loop regions with associated functions. This unique mechanism contrasts with the classical one involving a ligand-induced repositioning and stabilization of the C-terminal activation helix H12.

Insights into the activation mechanism of human estrogen-related receptor gamma by environmental endocrine disruptors.,Thouennon E, Delfosse V, Bailly R, Blanc P, Boulahtouf A, Grimaldi M, Barducci A, Bourguet W, Balaguer P Cell Mol Life Sci. 2019 May 24. pii: 10.1007/s00018-019-03129-x. doi:, 10.1007/s00018-019-03129-x. PMID:31127318<ref>PMID:31127318</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6i61" style="background-color:#fffaf0;"></div>

==See Also==
*[[Estrogen-related receptor 3D structures|Estrogen-related receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blanc P]]
[[Category: Bourguet W]]
[[Category: Delfosse V]]