6hl1
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Farnesoid X receptor (FXR) with bound NCoA-2 peptide and CDCA== | |
| + | <StructureSection load='6hl1' size='340' side='right'caption='[[6hl1]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hl1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4qe6 4qe6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HL1 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]] 1.599Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JN3:CHENODEOXYCHOLIC+ACID'>JN3</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=6hl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl1 OCA], [https://pdbe.org/6hl1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hl1 RCSB], [https://www.ebi.ac.uk/pdbsum/6hl1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl1 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 == | ||
| + | The bile acid-sensing transcription factor farnesoid X receptor (FXR) regulates multiple metabolic processes. Modulation of FXR is desired to overcome several metabolic pathologies but pharmacological administration of full FXR agonists has been plagued by mechanism-based side effects. We have developed a modulator that partially activates FXR in vitro and in mice. Here we report the elucidation of the molecular mechanism that drives partial FXR activation by crystallography- and NMR-based structural biology. Natural and synthetic FXR agonists stabilize formation of an extended helix alpha11 and the alpha11-alpha12 loop upon binding. This strengthens a network of hydrogen bonds, repositions helix alpha12 and enables co-activator recruitment. Partial agonism in contrast is conferred by a kink in helix alpha11 that destabilizes the alpha11-alpha12 loop, a critical determinant for helix alpha12 orientation. Thereby, the synthetic partial agonist induces conformational states, capable of recruiting both co-repressors and co-activators leading to an equilibrium of co-activator and co-repressor binding. | ||
| - | + | Molecular tuning of farnesoid X receptor partial agonism.,Merk D, Sreeramulu S, Kudlinzki D, Saxena K, Linhard V, Gande SL, Hiller F, Lamers C, Nilsson E, Aagaard A, Wissler L, Dekker N, Bamberg K, Schubert-Zsilavecz M, Schwalbe H Nat Commun. 2019 Jul 2;10(1):2915. doi: 10.1038/s41467-019-10853-2. PMID:31266946<ref>PMID:31266946</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6hl1" style="background-color:#fffaf0;"></div> |
| - | [[Category: Kudlinzki | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: Schwalbe | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kudlinzki D]] | ||
| + | [[Category: Linhard VL]] | ||
| + | [[Category: Merk D]] | ||
| + | [[Category: Saxena K]] | ||
| + | [[Category: Schubert-Zsilavecz M]] | ||
| + | [[Category: Schwalbe H]] | ||
Current revision
Crystal Structure of Farnesoid X receptor (FXR) with bound NCoA-2 peptide and CDCA
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