7vue
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structural insight of the molecular mechanism of cilofexor bound to FXR== | |
| + | <StructureSection load='7vue' size='340' side='right'caption='[[7vue]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7vue]] is a 2 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=7VUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VUE 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]] 2.601Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=811:2-[3-[4-[[3-[2,6-bis(chloranyl)phenyl]-5-cyclopropyl-1,2-oxazol-4-yl]methoxy]-2-chloranyl-phenyl]-3-oxidanyl-azetidin-1-yl]pyridine-4-carboxylic+acid'>811</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=7vue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vue OCA], [https://pdbe.org/7vue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vue RCSB], [https://www.ebi.ac.uk/pdbsum/7vue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vue ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Farnesoid X receptor (FXR) is a bile acid-related nuclear receptor and is considered a promising target to treat several liver disorders. Cilofexor is a selective FXR agonist and has already entered phase III trials in primary sclerosing cholangitis (PSC) patients. Pruritis caused by cilofexor treatment is dose dependent. The binding characteristics of cilofexor with FXR and its pruritogenic mechanism remain unclear. In our research, the affinity of cilofexor bound to FXR was detected using an isothermal titration calorimetry (ITC) assay. The binding mechanism between cilofexor and FXR-LBD is explained by the cocrystal structure of the FXR/cilofexor complex. Structural models indicate the possibility that cilofexor activates Mas-related G protein-coupled receptor X4 (MRGPRX4) or G protein-coupled bile acid receptor 1 (GPBAR1), leading to pruritus. In summary, our analyses provide a molecular mechanism of cilofexor binding to FXR and provide a possible explanation for the dose-dependent pruritis of cilofexor. | ||
| - | + | Structural insight into the molecular mechanism of cilofexor binding to the farnesoid X receptor.,Jiang L, Liu X, Wei H, Dai S, Qu L, Chen X, Guo M, Chen Y Biochem Biophys Res Commun. 2022 Mar 5;595:1-6. doi: 10.1016/j.bbrc.2022.01.069. , Epub 2022 Jan 21. PMID:35091108<ref>PMID:35091108</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Chen | + | <div class="pdbe-citations 7vue" style="background-color:#fffaf0;"></div> |
| - | [[Category: Jiang | + | |
| + | ==See Also== | ||
| + | *[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Chen YC]] | ||
| + | [[Category: Jiang L]] | ||
Current revision
Structural insight of the molecular mechanism of cilofexor bound to FXR
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