3d90

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[[Image:3d90.png|left|200px]]
 
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{{STRUCTURE_3d90| PDB=3d90 | SCENE= }}
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==Crystal structure of the human progesterone receptor ligand-binding domain bound to levonorgestrel==
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<StructureSection load='3d90' size='340' side='right'caption='[[3d90]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3d90]] 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=3D90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D90 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]] 2.26&#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=NOG:13-BETA-ETHYL-17-ALPHA-ETHYNYL-17-BETA-HYDROXYGON-4-EN-3-ONE'>NOG</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=3d90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d90 OCA], [https://pdbe.org/3d90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d90 RCSB], [https://www.ebi.ac.uk/pdbsum/3d90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d90 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/d9/3d90_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=3d90 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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Many progestins have been developed for use in contraception, menopausal hormone therapy, and treatment of gynecological diseases. They are derived from either progesterone or testosterone, and they act by binding to the progesterone receptor (PR), a hormone-inducible transcription factor belonging to the nuclear receptor superfamily. Unlike mineralocorticoid, glucocorticoid, and androgen receptors, the steroid-receptor contacts that trigger the switch of the ligand-binding domain from an inactive to an active conformation have not yet been identified for the PR. With this aim, we solved the crystal structure of the ligand-binding domain of the human PR complexed with levonorgestrel, a potent testosterone-derived progestin characterized by a 13-ethyl substituent. Via mutagenesis analysis and functional studies, we identified Met909 of the helix 12 as the key residue for PR activation by both testosterone- and progesterone-derived progestins with a 13-methyl or a 13-ethyl substituent. We also showed that Asn719 contributes to PR activation by testosterone-derived progestins only, and that Met759 and Met909 are responsible for the high potency of 19-norprogestins and of 13-ethyl progestins, respectively. Our findings provide a structural guideline for the rational synthesis of potent PR agonist and antagonist ligands that could have therapeutic uses in women's health.
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===Crystal structure of the human progesterone receptor ligand-binding domain bound to levonorgestrel===
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Met909 plays a key role in the activation of the progesterone receptor and also in the high potency of 13-ethyl progestins.,Petit-Topin I, Turque N, Fagart J, Fay M, Ulmann A, Gainer E, Rafestin-Oblin ME Mol Pharmacol. 2009 Jun;75(6):1317-24. Epub 2009 Mar 16. PMID:19289570<ref>PMID:19289570</ref>
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{{ABSTRACT_PUBMED_19289570}}
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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 3d90" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[3d90]] 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=3D90 OCA].
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*[[Progesterone receptor|Progesterone receptor]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019289570</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Fagart, J.]]
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[[Category: Large Structures]]
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[[Category: Gainer, E.]]
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[[Category: Fagart J]]
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[[Category: Petit-Topin, I.]]
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[[Category: Gainer E]]
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[[Category: Rafestin-Oblin, M E.]]
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[[Category: Petit-Topin I]]
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[[Category: Turque, N.]]
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[[Category: Rafestin-Oblin ME]]
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[[Category: Ulman, A.]]
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[[Category: Turque N]]
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[[Category: Contraception]]
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[[Category: Ulman A]]
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[[Category: Dna-binding]]
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[[Category: Lipid-binding]]
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[[Category: Metal-binding]]
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[[Category: Nuclear receptor]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Progesterone receptor]]
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[[Category: Receptor]]
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[[Category: Steroid receptor]]
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[[Category: Steroid-binding]]
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[[Category: Transcription]]
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[[Category: Transcription factor]]
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[[Category: Transcription regulation]]
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[[Category: Women health]]
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[[Category: Zinc-finger]]
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Current revision

Crystal structure of the human progesterone receptor ligand-binding domain bound to levonorgestrel

PDB ID 3d90

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