1n83

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[[Image:1n83.gif|left|200px]]
 
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{{Structure
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==Crystal Structure of the complex between the Orphan Nuclear Hormone Receptor ROR(alpha)-LBD and Cholesterol==
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|PDB= 1n83 |SIZE=350|CAPTION= <scene name='initialview01'>1n83</scene>, resolution 1.63&Aring;
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<StructureSection load='1n83' size='340' side='right'caption='[[1n83]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>
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<table><tr><td colspan='2'>[[1n83]] is a 1 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=1N83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N83 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]] 1.63&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene></td></tr>
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|DOMAIN=
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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=1n83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n83 OCA], [https://pdbe.org/1n83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n83 RCSB], [https://www.ebi.ac.uk/pdbsum/1n83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n83 ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n83 OCA], [http://www.ebi.ac.uk/pdbsum/1n83 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n83 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/RORA_HUMAN RORA_HUMAN] Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives.<ref>PMID:9862959</ref> <ref>PMID:11554739</ref> <ref>PMID:11053433</ref> <ref>PMID:14570920</ref> <ref>PMID:15790933</ref> <ref>PMID:15781255</ref> <ref>PMID:17512500</ref> <ref>PMID:18658046</ref> <ref>PMID:18005000</ref> <ref>PMID:12467577</ref>
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== Evolutionary Conservation ==
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'''Crystal Structure of the complex between the Orphan Nuclear Hormone Receptor ROR(alpha)-LBD and Cholesterol'''
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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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==Overview==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n8/1n83_consurf.spt"</scriptWhenChecked>
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The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. No X-ray structure of RORalpha has been described so far, and no ligand has been identified. We describe the first crystal structure of the ligand binding domain (LBD) of RORalpha, at 1.63 A resolution. This structure revealed a ligand present in the ligand binding pocket (LBP), which was identified by X-ray crystallography as cholest-5-en-3beta-ol (cholesterol). Moreover, RORalpha transcriptional activity could be modulated by changes in intracellular cholesterol level or mutation of residues involved in cholesterol binding. These findings suggest that RORalpha could play a key role in the regulation of cholesterol homeostasis and thus represents an important drug target in cholesterol-related diseases.
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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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==About this Structure==
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</jmolCheckbox>
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1N83 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N83 OCA].
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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=1n83 ConSurf].
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<div style="clear:both"></div>
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==Reference==
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== References ==
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X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha., Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B, Structure. 2002 Dec;10(12):1697-707. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12467577 12467577]
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bitsch, F.]]
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[[Category: Bitsch F]]
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[[Category: Delhon, I.]]
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[[Category: Delhon I]]
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[[Category: Fournier, B.]]
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[[Category: Fournier B]]
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[[Category: Geiser, M.]]
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[[Category: Geiser M]]
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[[Category: Geisse, S.]]
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[[Category: Geisse S]]
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[[Category: Kallen, J A.]]
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[[Category: Kallen JA]]
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[[Category: Schlaeppi, J M.]]
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[[Category: Schlaeppi JM]]
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[[Category: dna binding]]
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[[Category: nuclear protein]]
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[[Category: receptor]]
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[[Category: three-layered alpha helical sandwich]]
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[[Category: transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:26:47 2008''
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Current revision

Crystal Structure of the complex between the Orphan Nuclear Hormone Receptor ROR(alpha)-LBD and Cholesterol

PDB ID 1n83

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OCA

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