7d42

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(New page: '''Unreleased structure''' The entry 7d42 is ON HOLD until Paper Publication Authors: Jiang, L., Chen, Y. Description: Structural basis of tropifexor as a potent and selective agonist ...)
Current revision (16:26, 29 November 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 7d42 is ON HOLD until Paper Publication
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==Structural basis of tropifexor as a potent and selective agonist for farnesoid X receptor==
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<StructureSection load='7d42' size='340' side='right'caption='[[7d42]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7d42]] 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=7D42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D42 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.697&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GWF:Tropifexor'>GWF</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7d42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d42 OCA], [https://pdbe.org/7d42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d42 RCSB], [https://www.ebi.ac.uk/pdbsum/7d42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d42 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Farnesoid X receptor (FXR) is considered as a potential target for the treatment of several liver disorders such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Tropifexor is a highly potent and non-steroidal FXR agonist that has progressed into phase II clinical trials in patients with PBC. The clinical trials demonstrate that tropifexor improved serum markers of patients with liver diseases and lower side effect such as pruritus that might be implicated with TGR5 activation. However, the molecular mechanism of the potency and selectivity of tropifexor remains unclear. In this study, the binding affinity of FXR and tropifexor is measured by isothermal titration calorimetry (ITC) assays. The crystal structure of the FXR/tropifexor complex is determined at 2.7 A resolution to explain the molecular mechanism of tropifexor bound to FXR-LBD. Structural comparison with other FXR/agonists structures reveals the conformational change in the FXR/tropifexor structure. Moreover the structural superposition of TGR5/tropifexor indicates that the steric hindrance between tropifexor and TGR5 might be a possible explanation for the impotency arises of tropifexor to TGR5. Overall, our analyses might provide an insight into the molecular mechanism of tropifexor binding to FXR-LBD and account for the high selectivity of tropifexor for FXR versus TGR5.
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Authors: Jiang, L., Chen, Y.
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Structural basis of tropifexor as a potent and selective agonist of farnesoid X receptor.,Jiang L, Xiao D, Li Y, Dai S, Qu L, Chen X, Guo M, Wei H, Chen Y Biochem Biophys Res Commun. 2021 Jan 1;534:1047-1052. doi: , 10.1016/j.bbrc.2020.10.039. Epub 2020 Oct 26. PMID:33121679<ref>PMID:33121679</ref>
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Description: Structural basis of tropifexor as a potent and selective agonist for farnesoid X receptor
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Jiang, L]]
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<div class="pdbe-citations 7d42" style="background-color:#fffaf0;"></div>
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[[Category: Chen, Y]]
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==See Also==
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*[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Chen Y]]
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[[Category: Jiang L]]

Current revision

Structural basis of tropifexor as a potent and selective agonist for farnesoid X receptor

PDB ID 7d42

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