4x1g: Difference between revisions

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-'''Unreleased structure'''
-The entry 4x1g is ON HOLD  until Paper Publication
+==Crystal structure of the hPXR-LBD in complex with the synthetic estrogen 17alpha-ethinylestradiol and the pesticide trans-nonachlor==
+<StructureSection load='4x1g' size='340' side='right'caption='[[4x1g]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4x1g]] 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=4X1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X1G 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]] 2.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3WF:ETHINYL+ESTRADIOL'>3WF</scene>, <scene name='pdbligand=3WG:TRANS-NONACHLOR'>3WG</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=4x1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x1g OCA], [https://pdbe.org/4x1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x1g RCSB], [https://www.ebi.ac.uk/pdbsum/4x1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x1g ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN] Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.<ref>PMID:9727070</ref> <ref>PMID:11668216</ref> <ref>PMID:11297522</ref> <ref>PMID:19297428</ref> <ref>PMID:12578355</ref> <ref>PMID:18768384</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of 'supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.
-Authors: DELFOSSE, V., HUET, T., BOURGUET, W.
+Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.,Delfosse V, Dendele B, Huet T, Grimaldi M, Boulahtouf A, Gerbal-Chaloin S, Beucher B, Roecklin D, Muller C, Rahmani R, Cavailles V, Daujat-Chavanieu M, Vivat V, Pascussi JM, Balaguer P, Bourguet W Nat Commun. 2015 Sep 3;6:8089. doi: 10.1038/ncomms9089. PMID:26333997<ref>PMID:26333997</ref>
-Description: Crystal structure of the hPXR-LBD in complex with the synthetic estrogen 17alpha-ethinylestradiol and the pesticide trans-nonachlor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Delfosse, V]]
+<div class="pdbe-citations 4x1g" style="background-color:#fffaf0;"></div>
-[[Category: Bourguet, W]]
-[[Category: Huet, T]]
+==See Also==
+*[[Pregnane X receptor 3D structures|Pregnane X receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bourguet W]]
+[[Category: Delfosse V]]
+[[Category: Huet T]]