1fcy

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{{Seed}}
 
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[[Image:1fcy.png|left|200px]]
 
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==ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564==
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The line below this paragraph, containing "STRUCTURE_1fcy", creates the "Structure Box" on the page.
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<StructureSection load='1fcy' size='340' side='right'caption='[[1fcy]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1fcy]] 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=1FCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FCY FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.3&#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=564:6-(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRO-NAPHTALENE-2-CARBONYL)-NAPHTALENE-2-CARBOXYLIC+ACID'>564</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
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{{STRUCTURE_1fcy| PDB=1fcy | SCENE= }}
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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=1fcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fcy OCA], [https://pdbe.org/1fcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fcy RCSB], [https://www.ebi.ac.uk/pdbsum/1fcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fcy ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RARG_HUMAN RARG_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (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/fc/1fcy_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=1fcy ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human retinoic acid receptor (hRAR) belongs to the family of nuclear receptors that regulate transcription in a ligand-dependent way. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids that are involved in the treatment of various skin diseases and cancers, in particular breast cancer and acute promyelocytic leukemia. Therefore, synthetic retinoids have been developed aiming at isotype selectivity and reduced side-effects. We report the crystal structures of three complexes of the hRARgamma ligand-binding domain (LBD) bound to agonist retinoids that possess selectivity either for RARgamma (BMS184394) or for RARbeta/gamma (CD564), or that are potent for all RAR-isotypes (panagonist BMS181156). The high resolution data (1.3-1. 5 A) provide a description at the atomic level of the ligand pocket revealing the molecular determinants for the different degrees of ligand selectivity. The comparison of the complexes of the chemically closely related retinoids BMS184394 and CD564 shows that the side-chain of Met272 adopts different conformations depending on the presence of a hydrogen bond between its sulfur atom and the ligand. This accounts for their different isotype selectivity. On the other hand, the difference between the pan- and the RARbeta, gamma-selective agonist is probably due to a steric discrimination at the level of the 2-naphthoic acid moiety of CD564. Based on this study, we propose a model for a complex with the RARgamma-specific agonist CD666 that shows the possible applications for structure-based drug design of RAR isotype-selective retinoids.
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===ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564===
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Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.,Klaholz BP, Mitschler A, Moras D J Mol Biol. 2000 Sep 8;302(1):155-70. PMID:10964567<ref>PMID:10964567</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 1fcy" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_10964567}}, adds the Publication Abstract to the page
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*[[Retinoic acid receptor 3D structures|Retinoic acid receptor 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 10964567 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_10964567}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1FCY 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=1FCY OCA].
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==Reference==
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Structural basis for isotype selectivity of the human retinoic acid nuclear receptor., Klaholz BP, Mitschler A, Moras D, J Mol Biol. 2000 Sep 8;302(1):155-70. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10964567 10964567]
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[[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: Klaholz, B P.]]
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[[Category: Klaholz BP]]
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[[Category: Mitschler, A.]]
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[[Category: Mitschler A]]
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[[Category: Moras, D.]]
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[[Category: Moras D]]
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[[Category: SPINE, Structural Proteomics in Europe.]]
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[[Category: Antiparallel alpha-helical sandwich fold]]
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[[Category: Drug design]]
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[[Category: Isotype selectivity]]
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[[Category: Retinoid ligand complex]]
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[[Category: Spine]]
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[[Category: Structural genomic]]
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[[Category: Structural proteomics in europe]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:03:56 2008''
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Current revision

ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564

PDB ID 1fcy

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