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6hl0

From Proteopedia

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'''Unreleased structure'''
 
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The entry 6hl0 is ON HOLD until Paper Publication
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==Crystal Structure of Farnesoid X receptor (FXR) with bound NCoA-2 peptide==
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<StructureSection load='6hl0' size='340' side='right'caption='[[6hl0]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6hl0]] 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=6HL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HL0 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]] 1.66&#8491;</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=6hl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl0 OCA], [https://pdbe.org/6hl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hl0 RCSB], [https://www.ebi.ac.uk/pdbsum/6hl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl0 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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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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Authors: Kudlinzki, D., Merk, D., Linhard, V.L., Saxena, K., Schubert-Zsilavecz, M., Schwalbe, H.
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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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Description: Crystal Structure of Farnesoid X receptor (FXR) with bound NCoA-2 peptide
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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: Linhard, V.L]]
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<div class="pdbe-citations 6hl0" style="background-color:#fffaf0;"></div>
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[[Category: Kudlinzki, D]]
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[[Category: Saxena, K]]
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==See Also==
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[[Category: Schubert-Zsilavecz, M]]
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*[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]]
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[[Category: Merk, D]]
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== References ==
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[[Category: Schwalbe, H]]
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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: Kudlinzki D]]
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[[Category: Linhard VL]]
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[[Category: Merk D]]
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[[Category: Saxena K]]
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[[Category: Schubert-Zsilavecz M]]
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[[Category: Schwalbe H]]

Current revision

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

PDB ID 6hl0

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