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5g3j
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5g3j is ON HOLD until Paper Publication Authors: Berger, M., Edman, K., Wissler, L., Neuhaus, R., Rehwinkel, H., Schacke, H., Jaroch, S. Descriptio...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Discovery of New Selective Glucocorticoid Receptor Agonist Leads== | |
| + | <StructureSection load='5g3j' size='340' side='right'caption='[[5g3j]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5g3j]] 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=5G3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G3J 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]] 2.4Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=E7T:5-[[(1S,2R,4R)-4-ETHYL-6,7-BIS(FLUORANYL)-2,5-BIS(OXIDANYL)-2-(TRIFLUOROMETHYL)-3,4-DIHYDRO-1H-NAPHTHALEN-1-YL]AMINO]-1H-QUINOLIN-2-ONE'>E7T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5g3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g3j OCA], [https://pdbe.org/5g3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g3j RCSB], [https://www.ebi.ac.uk/pdbsum/5g3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g3j 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 == | ||
| + | We report on the discovery of two new lead series for the development of glucocorticoid receptor agonists. Firstly, the discovery of tetrahydronaphthalenes led to metabolically stable and dissociated compounds. Their binding mode to the glucocorticoid receptor could be elucidated through an X-ray structure. Closer inspection into the reaction path and analyses of side products revealed a new amino alcohol series also addressing the glucocorticoid receptor and demonstrating strong anti-inflammatory activity in vitro. | ||
| - | + | Discovery of new selective glucocorticoid receptor agonist leads.,Berger M, Rehwinkel H, Schmees N, Schacke H, Edman K, Wissler L, Reichel A, Jaroch S Bioorg Med Chem Lett. 2017 Feb 1;27(3):437-442. doi: 10.1016/j.bmcl.2016.12.047. , Epub 2016 Dec 23. PMID:28043796<ref>PMID:28043796</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5g3j" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: Neuhaus | + | <references/> |
| - | [[Category: Rehwinkel | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Berger M]] | ||
| + | [[Category: Edman K]] | ||
| + | [[Category: Jaroch S]] | ||
| + | [[Category: Neuhaus R]] | ||
| + | [[Category: Rehwinkel H]] | ||
| + | [[Category: Schacke H]] | ||
| + | [[Category: Wissler L]] | ||
Current revision
Discovery of New Selective Glucocorticoid Receptor Agonist Leads
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Categories: Homo sapiens | Large Structures | Berger M | Edman K | Jaroch S | Neuhaus R | Rehwinkel H | Schacke H | Wissler L
