5g3j
From Proteopedia
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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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5G3J FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5g3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g3j OCA], [http://pdbe.org/5g3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g3j RCSB], [http://www.ebi.ac.uk/pdbsum/5g3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g3j ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN]] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[http://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> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. | ||
| + | == Function == | ||
| + | [[http://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> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</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> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5g3j" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Berger, M]] | ||
[[Category: Edman, K]] | [[Category: Edman, K]] | ||
[[Category: Jaroch, S]] | [[Category: Jaroch, S]] | ||
| - | [[Category: Schacke, H]] | ||
| - | [[Category: Wissler, L]] | ||
| - | [[Category: Berger, M]] | ||
[[Category: Neuhaus, R]] | [[Category: Neuhaus, R]] | ||
[[Category: Rehwinkel, H]] | [[Category: Rehwinkel, H]] | ||
| + | [[Category: Schacke, H]] | ||
| + | [[Category: Wissler, L]] | ||
| + | [[Category: Dna binding protein]] | ||
| + | [[Category: Glucocorticoid receptor]] | ||
| + | [[Category: Ligand complex]] | ||
| + | [[Category: Nuclear hormone receptor]] | ||
| + | [[Category: Peptide complex]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Steroid receptor]] | ||
Revision as of 17:35, 10 March 2017
Discovery of New Selective Glucocorticoid Receptor Agonist Leads
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