View source for 5nfp


==Glucocorticoid Receptor in complex with budesonide==
<StructureSection load='5nfp' size='340' side='right'caption='[[5nfp]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nfp]] 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=5NFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NFP 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8W5:(1~{S},2~{S},4~{R},6~{R},8~{S},9~{S},11~{S},12~{S},13~{R})-9,13-dimethyl-11-oxidanyl-8-(2-oxidanylethanoyl)-6-propyl-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosa-14,17-dien-16-one'>8W5</scene>, <scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5nfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nfp OCA], [https://pdbe.org/5nfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nfp RCSB], [https://www.ebi.ac.uk/pdbsum/5nfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nfp 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A class of potent, non-steroidal, selective indazole ether based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment of respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft drug strategy was implemented to ensure rapid elimination of drug candidates and minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate 15m (AZD7594) that demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged inhibition of lung edema, indicating potential for once-daily treatment.

Selective Non-steroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases.,Hemmerling M, Nilsson S, Edman K, Eirefelt S, Russell W, Hendrickx R, Johnsson E, Karrman-Mardh C, Berger M, Rehwinkel H, Abrahamsson A, Dahm Eacute N J, Eriksson AR, Gabos B, Henriksson K, Hossain N, Ivanova S, Jansson AH, Jensen TJ, Jerre A, Johansson H, Klingstedt T, Lepisto M, Lindsjo M, Mile I, Nikitidis G, Steele J, Tehler U, Wissler L, Hansson T J Med Chem. 2017 Sep 22. doi: 10.1021/acs.jmedchem.7b01215. PMID:28937774<ref>PMID:28937774</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nfp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucocorticoid receptor|Glucocorticoid receptor]]
*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Edman K]]
[[Category: Wissler L]]