2q3y

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[[Image:2q3y.jpg|left|200px]]
 
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{{Structure
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==Ancestral Corticiod Receptor in Complex with DOC==
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|PDB= 2q3y |SIZE=350|CAPTION= <scene name='initialview01'>2q3y</scene>, resolution 2.40&Aring;
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<StructureSection load='2q3y' size='340' side='right'caption='[[2q3y]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=1CA:DESOXYCORTICOSTERONE'>1CA</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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<table><tr><td colspan='2'>[[2q3y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q3Y 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]] 2.4&#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=1CA:DESOXYCORTICOSTERONE'>1CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3y OCA], [https://pdbe.org/2q3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q3y RCSB], [https://www.ebi.ac.uk/pdbsum/2q3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q3y ProSAT]</span></td></tr>
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</table>
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'''Ancestral Corticiod Receptor in Complex with DOC'''
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== Disease ==
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[https://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:11136233</ref>
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== Function ==
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==Overview==
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[https://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.<ref>PMID:14752053</ref>
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The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein-the approximately 450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations-substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes-played a major role in determining GR's evolutionary trajectory.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Disease==
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Check<jmol>
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Known diseases associated with this structure: Obesity, mild, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604630 604630]]
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q3/2q3y_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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2Q3Y is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3Y OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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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=2q3y ConSurf].
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Crystal structure of an ancient protein: evolution by conformational epistasis., Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW, Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17702911 17702911]
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<div style="clear:both"></div>
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[[Category: Single protein]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Unidentified]]
[[Category: Unidentified]]
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[[Category: Bridgham, J T.]]
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[[Category: Bridgham JT]]
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[[Category: Ortlund, E A.]]
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[[Category: Ortlund EA]]
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[[Category: Redinbo, M R.]]
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[[Category: Redinbo MR]]
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[[Category: Thornton, J W.]]
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[[Category: Thornton JW]]
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[[Category: 1CA]]
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[[Category: GOL]]
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[[Category: cortisol]]
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[[Category: doc]]
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[[Category: evolution]]
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[[Category: ligand binding domain]]
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[[Category: mineralocoticiod]]
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[[Category: nuclear receptor]]
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[[Category: transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:21:20 2008''
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Current revision

Ancestral Corticiod Receptor in Complex with DOC

PDB ID 2q3y

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