1ot7

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[[Image:1ot7.gif|left|200px]]
 
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{{Structure
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==Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR==
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|PDB= 1ot7 |SIZE=350|CAPTION= <scene name='initialview01'>1ot7</scene>, resolution 2.90&Aring;
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<StructureSection load='1ot7' size='340' side='right'caption='[[1ot7]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=IU5:ISO-URSODEOXYCHOLIC+ACID'>IU5</scene> and <scene name='pdbligand=CHC:6-ETHYL-CHENODEOXYCHOLIC ACID'>CHC</scene>
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<table><tr><td colspan='2'>[[1ot7]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=1OT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OT7 FirstGlance]. <br>
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|ACTIVITY=
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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]] 2.9&#8491;</td></tr>
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|GENE= NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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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>, <scene name='pdbligand=IU5:ISO-URSODEOXYCHOLIC+ACID'>IU5</scene></td></tr>
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}}
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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=1ot7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ot7 OCA], [https://pdbe.org/1ot7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ot7 RCSB], [https://www.ebi.ac.uk/pdbsum/1ot7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ot7 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/ot/1ot7_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=1ot7 ConSurf].
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<div style="clear:both"></div>
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'''Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR'''
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==See Also==
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*[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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==About this Structure==
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1OT7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OT7 OCA].
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==Reference==
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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://www.ncbi.nlm.nih.gov/pubmed/12718893 12718893]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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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 JM]]
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[[Category: Harp, J M.]]
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[[Category: Khorasanizadeh S]]
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[[Category: Khorasanizadeh, S.]]
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[[Category: Mi LZ]]
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[[Category: Mi, L Z.]]
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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 TM]]
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[[Category: Willson, T M.]]
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[[Category: CHC]]
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[[Category: IU5]]
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[[Category: bile acid]]
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[[Category: coactivator]]
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[[Category: fxr]]
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[[Category: ligand binding domain]]
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[[Category: nuclear receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:15:16 2008''
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Current revision

Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR

PDB ID 1ot7

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