1sqn

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{{STRUCTURE_1sqn| PDB=1sqn | SCENE= }}
 
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===Progesterone Receptor Ligand Binding Domain with bound Norethindrone===
 
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{{ABSTRACT_PUBMED_15189034}}
 
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==Function==
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==Progesterone Receptor Ligand Binding Domain with bound Norethindrone==
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[[http://www.uniprot.org/uniprot/PRGR_HUMAN PRGR_HUMAN]] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref> Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref>
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<StructureSection load='1sqn' size='340' side='right'caption='[[1sqn]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1sqn]] is a 2 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=1SQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SQN 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]] 1.451&#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=NDR:(14BETA,17ALPHA)-17-ETHYNYL-17-HYDROXYESTR-4-EN-3-ONE'>NDR</scene></td></tr>
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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=1sqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sqn OCA], [https://pdbe.org/1sqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sqn RCSB], [https://www.ebi.ac.uk/pdbsum/1sqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sqn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PRGR_HUMAN PRGR_HUMAN] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref> Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</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/sq/1sqn_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=1sqn 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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Although progesterone, the natural ligand of the progesterone receptor (PR), has a hydrogen atom at the 17alpha position, other potent steroid agonists such as norethindrone and mometasone furoate have larger substituents at this position that are accommodated by the PR ligand binding pocket. Crystallographic analysis of PR ligand binding domain complexes clearly demonstrated that these moieties were accommodated by local shifts of the protein main chain and by adoption of alternative side chain rotamer conformations of ligand-proximal amino acids. These conformational changes imparted a ligand-specific volume to the binding pocket, from 490 A3 in the metribolone complex to 520 A3 in the norethindrone complex, 565 A3 in the progesterone complex, and 730 A3 in the mometasone furoate complex. Despite these marked alterations in binding pocket volume, critical interactions essential for establishment of an active AF2 conformation were maintained.
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==About this Structure==
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Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes.,Madauss KP, Deng SJ, Austin RJ, Lambert MH, McLay I, Pritchard J, Short SA, Stewart EL, Uings IJ, Williams SP J Med Chem. 2004 Jun 17;47(13):3381-7. PMID:15189034<ref>PMID:15189034</ref>
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[[1sqn]] is a 2 chain structure with 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=1SQN OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:015189034</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 1sqn" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Progesterone receptor|Progesterone receptor]]
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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: Austin, R J.H.]]
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[[Category: Large Structures]]
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[[Category: Deng, J S.]]
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[[Category: Austin RJH]]
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[[Category: Lambert, M H.]]
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[[Category: Deng J-S]]
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[[Category: Madauss, K P.]]
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[[Category: Lambert MH]]
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[[Category: McLay, I.]]
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[[Category: Madauss KP]]
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[[Category: Pritchard, J.]]
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[[Category: McLay I]]
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[[Category: Short, S A.]]
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[[Category: Pritchard J]]
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[[Category: Stewart, E L.]]
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[[Category: Short SA]]
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[[Category: Uings, I J.]]
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[[Category: Stewart EL]]
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[[Category: Williams, S P.]]
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[[Category: Uings IJ]]
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[[Category: Birth control]]
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[[Category: Williams SP]]
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[[Category: Hormone-growth factor receptor complex]]
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[[Category: Norethindrone]]
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[[Category: Nuclear receptor]]
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[[Category: Progesterone receptor]]
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[[Category: Steroid receptor]]
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Current revision

Progesterone Receptor Ligand Binding Domain with bound Norethindrone

PDB ID 1sqn

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