1osv

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(New page: 200px<br /><applet load="1osv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1osv, resolution 2.50&Aring;" /> '''STRUCTURAL BASIS FOR...)
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[[Image:1osv.gif|left|200px]]<br /><applet load="1osv" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1osv, resolution 2.50&Aring;" />
 
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'''STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR'''<br />
 
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==Overview==
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==STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR==
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The nuclear receptor FXR is the sensor of physiological levels of, enterohepatic bile acids, the end products of cholesterol catabolism. Here, we report crystal structures of the FXR ligand binding domain in complex, with coactivator peptide and two different bile acids. An unusual A/B ring, juncture, a feature associated with bile acids and no other steroids, provides ligand discrimination and triggers a pi-cation switch that, activates FXR. Helix 12, the activation function 2 of the receptor, adopts, the agonist conformation and stabilizes coactivator peptide binding. FXR, is able to interact simultaneously with two coactivator motifs, providing, a mechanism for enhanced binding of coactivators through intermolecular, contacts between their LXXLL sequences. These FXR complexes provide direct, insights into the design of therapeutic bile acids for treatment of, hyperlipidemia and cholestasis.
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<StructureSection load='1osv' size='340' side='right'caption='[[1osv]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1osv]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OSV 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]] 2.5&#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=CHC:6-ETHYL-CHENODEOXYCHOLIC+ACID'>CHC</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=1osv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osv OCA], [https://pdbe.org/1osv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1osv RCSB], [https://www.ebi.ac.uk/pdbsum/1osv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1osv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NR1H4_RAT NR1H4_RAT] 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) and activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 within its gene locus (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osv_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1osv ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1OSV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CHC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OSV OCA].
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*[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural basis for bile acid binding and activation of the nuclear receptor FXR., Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F, Mol Cell. 2003 Apr;11(4):1093-100. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12718893 12718893]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Devarakonda, S.]]
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[[Category: Devarakonda S]]
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[[Category: Han, Q.]]
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[[Category: Han Q]]
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[[Category: Harp, J.M.]]
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[[Category: Harp JM]]
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[[Category: Khorasanizadeh, S.]]
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[[Category: Khorasanizadeh S]]
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[[Category: Mi, L.Z.]]
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[[Category: Mi LZ]]
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[[Category: Pellicciari, R.]]
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[[Category: Pellicciari R]]
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[[Category: Rastinejad, F.]]
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[[Category: Rastinejad F]]
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[[Category: Willson, T.M.]]
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[[Category: Willson TM]]
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[[Category: CHC]]
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[[Category: bile acid]]
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[[Category: coactivator]]
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[[Category: lbd]]
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[[Category: nuclear receptor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:09:49 2007''
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STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR

PDB ID 1osv

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