View source for 3cld


==Ligand binding domain of the glucocorticoid receptor complexed with fluticazone furoate==
<StructureSection load='3cld' size='340' side='right'caption='[[3cld]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3cld]] is a 4 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=3CLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CLD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.84&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GW6:(6ALPHA,11ALPHA,14BETA,16ALPHA,17ALPHA)-6,9-DIFLUORO-17-{[(FLUOROMETHYL)SULFANYL]CARBONYL}-11-HYDROXY-16-METHYL-3-OXOANDROSTA-1,4-DIEN-17-YL+FURAN-2-CARBOXYLATE'>GW6</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cld OCA], [https://pdbe.org/3cld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cld RCSB], [https://www.ebi.ac.uk/pdbsum/3cld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cld ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[https://omim.org/entry/138040 138040]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref> <ref>PMID:1704018</ref> <ref>PMID:7683692</ref> <ref>PMID:11589680</ref> <ref>PMID:11701741</ref> 
== Function ==
[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cl/3cld_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3cld ConSurf].
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== Publication Abstract from PubMed ==
An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17alpha furoate ester to occupy more fully the lipophilic 17alpha pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.

X-ray Crystal Structure of the Novel Enhanced-Affinity Glucocorticoid Agonist Fluticasone Furoate in the Glucocorticoid Receptor-Ligand Binding Domain.,Biggadike K, Bledsoe RK, Hassell AM, Kirk BE, McLay IM, Shewchuk LM, Stewart EL J Med Chem. 2008 Jun 26;51(12):3349-52. Epub 2008 Jun 4. PMID:18522385<ref>PMID:18522385</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3cld" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Biggadike KB]]
[[Category: Bledsoe RK]]
[[Category: Hassell AM]]
[[Category: McLay I]]
[[Category: Shewchuk LM]]
[[Category: Stewart E]]