8r00
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the human PXR ligand-binding domain in complex with furanodienone== | |
| + | <StructureSection load='8r00' size='340' side='right'caption='[[8r00]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8r00]] 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=8R00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R00 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]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XFQ:3,6,10-trimethyl-8,11-dihydro-7~{H}-cyclodeca[b]furan-4-one'>XFQ</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=8r00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r00 OCA], [https://pdbe.org/8r00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r00 RCSB], [https://www.ebi.ac.uk/pdbsum/8r00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r00 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 == | ||
| + | The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases. | ||
| - | + | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.,Wang X, Zhang G, Bian Z, Chow V, Grimaldi M, Carivenc C, Sirounian S, Li H, Sladekova L, Motta S, Luperi Y, Gong Y, Costello C, Li L, Jachimowicz M, Guo M, Hu S, Wilson D, Balaguer P, Bourguet W, Mani S, Bonati L, Peng H, March J, Wang H, Wang S, Krause HM, Liu J Nat Commun. 2025 Feb 3;16(1):1280. doi: 10.1038/s41467-025-56624-0. PMID:39900639<ref>PMID:39900639</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8r00" style="background-color:#fffaf0;"></div> |
| - | [[Category: Carivenc | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bourguet W]] | ||
| + | [[Category: Carivenc C]] | ||
| + | [[Category: Sirounian S]] | ||
Current revision
Crystal structure of the human PXR ligand-binding domain in complex with furanodienone
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