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6hl1

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<StructureSection load='6hl1' size='340' side='right'caption='[[6hl1]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='6hl1' size='340' side='right'caption='[[6hl1]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6hl1]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HL1 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6hl1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HL1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JN3:CHENODEOXYCHOLIC+ACID'>JN3</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JN3:CHENODEOXYCHOLIC+ACID'>JN3</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qe6|4qe6]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qe6|4qe6]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1H4, BAR, FXR, HRR1, RIP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl1 OCA], [http://pdbe.org/6hl1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hl1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hl1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl1 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl1 OCA], [http://pdbe.org/6hl1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hl1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hl1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[[http://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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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6hl1" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Kudlinzki, D]]
[[Category: Kudlinzki, D]]

Revision as of 12:33, 17 July 2019

Crystal Structure of Farnesoid X receptor (FXR) with bound NCoA-2 peptide and CDCA

PDB ID 6hl1

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