1p93

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[[Image:1p93.gif|left|200px]]
 
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==CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR==
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The line below this paragraph, containing "STRUCTURE_1p93", creates the "Structure Box" on the page.
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<StructureSection load='1p93' size='340' side='right'caption='[[1p93]], [[Resolution|resolution]] 2.70&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'>[[1p93]] is a 8 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=1P93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P93 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]] 2.7&#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=DEX:DEXAMETHASONE'>DEX</scene></td></tr>
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{{STRUCTURE_1p93| PDB=1p93 | 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=1p93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p93 OCA], [https://pdbe.org/1p93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p93 RCSB], [https://www.ebi.ac.uk/pdbsum/1p93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p93 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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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/p9/1p93_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=1p93 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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Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 A resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 A. The RU-486 structure was solved in several different crystal forms, two with helix 12 intact (GR1 and GR3) and one with a protease-digested C terminus (GR2). In GR1, part of helix 12 is in a position that covers the co-activator pocket, whereas in the GR3, domain swapping is seen between the crystallographically identical subunits in the GR dimer. An arm consisting of the end of helix 11 and beyond stretches out from one molecule, and helix 12 binds to the other LBD, partly blocking the coactivator pocket of that molecule. This type of GR-LBD dimer has not been described before but might be an artifact from crystallization. Furthermore, the subunits of the GR3 dimers are covalently connected via a disulfide bond between the Cys-736 residues in the two molecules. All three RU-486 GR-LBD structures show that GR has a very flexible region between the end of helix 11 and the end of helix 12.
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'''CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR'''
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The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism.,Kauppi B, Jakob C, Farnegardh M, Yang J, Ahola H, Alarcon M, Calles K, Engstrom O, Harlan J, Muchmore S, Ramqvist AK, Thorell S, Ohman L, Greer J, Gustafsson JA, Carlstedt-Duke J, Carlquist M J Biol Chem. 2003 Jun 20;278(25):22748-54. Epub 2003 Apr 9. PMID:12686538<ref>PMID:12686538</ref>
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==Overview==
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Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 A resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 A. The RU-486 structure was solved in several different crystal forms, two with helix 12 intact (GR1 and GR3) and one with a protease-digested C terminus (GR2). In GR1, part of helix 12 is in a position that covers the co-activator pocket, whereas in the GR3, domain swapping is seen between the crystallographically identical subunits in the GR dimer. An arm consisting of the end of helix 11 and beyond stretches out from one molecule, and helix 12 binds to the other LBD, partly blocking the coactivator pocket of that molecule. This type of GR-LBD dimer has not been described before but might be an artifact from crystallization. Furthermore, the subunits of the GR3 dimers are covalently connected via a disulfide bond between the Cys-736 residues in the two molecules. All three RU-486 GR-LBD structures show that GR has a very flexible region between the end of helix 11 and the end of helix 12.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1P93 is a [[Protein complex]] structure of sequences 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=1P93 OCA].
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</div>
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<div class="pdbe-citations 1p93" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism., Kauppi B, Jakob C, Farnegardh M, Yang J, Ahola H, Alarcon M, Calles K, Engstrom O, Harlan J, Muchmore S, Ramqvist AK, Thorell S, Ohman L, Greer J, Gustafsson JA, Carlstedt-Duke J, Carlquist M, J Biol Chem. 2003 Jun 20;278(25):22748-54. Epub 2003 Apr 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12686538 12686538]
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*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
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== References ==
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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: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Ahola, H.]]
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[[Category: Ahola H]]
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[[Category: Alarcon, M.]]
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[[Category: Alarcon M]]
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[[Category: Calles, K.]]
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[[Category: Calles K]]
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[[Category: Carlquist, M.]]
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[[Category: Carlquist M]]
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[[Category: Carlstedt-Duke, J.]]
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[[Category: Carlstedt-Duke J]]
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[[Category: Engstrom, O.]]
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[[Category: Engstrom O]]
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[[Category: Farnegardh, M.]]
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[[Category: Farnegardh M]]
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[[Category: Greer, J.]]
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[[Category: Greer J]]
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[[Category: Gustafsson, J A.]]
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[[Category: Gustafsson J-A]]
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[[Category: Harlan, J.]]
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[[Category: Harlan J]]
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[[Category: Jakob, C.]]
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[[Category: Jakob C]]
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[[Category: Kauppi, B.]]
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[[Category: Kauppi B]]
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[[Category: Muchmore, S.]]
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[[Category: Muchmore S]]
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[[Category: Ohman, L.]]
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[[Category: Ohman L]]
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[[Category: Ramqvist, A K.]]
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[[Category: Ramqvist A-K]]
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[[Category: Thorell, S.]]
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[[Category: Thorell S]]
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[[Category: Yang, J.]]
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[[Category: Yang J]]
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[[Category: Anti parallel alpha helix sandwich]]
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[[Category: Protien-ligand complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:50:13 2008''
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CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR

PDB ID 1p93

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