4udc: Difference between revisions
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<StructureSection load='4udc' size='340' side='right'caption='[[4udc]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4udc' size='340' side='right'caption='[[4udc]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4udc]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4udc]] 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=4UDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UDC 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=DEX:DEXAMETHASONE'>DEX</scene> | </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=DEX:DEXAMETHASONE'>DEX</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=4udc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4udc OCA], [https://pdbe.org/4udc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4udc RCSB], [https://www.ebi.ac.uk/pdbsum/4udc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4udc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == 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 == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 22: | ||
==See Also== | ==See Also== | ||
*[[Glucocorticoid receptor|Glucocorticoid receptor]] | *[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Aagaard | [[Category: Aagaard A]] | ||
[[Category: Backstrom | [[Category: Backstrom S]] | ||
[[Category: Bjursell | [[Category: Bjursell M]] | ||
[[Category: Bodin | [[Category: Bodin C]] | ||
[[Category: Cavallin | [[Category: Cavallin A]] | ||
[[Category: Edman | [[Category: Edman K]] | ||
[[Category: Grebner | [[Category: Grebner C]] | ||
[[Category: Guallar | [[Category: Guallar V]] | ||
[[Category: Hogner | [[Category: Hogner A]] | ||
[[Category: Hussein | [[Category: Hussein A]] | ||
[[Category: Jellesmark-Jensen | [[Category: Jellesmark-Jensen T]] | ||
[[Category: Karlsson | [[Category: Karlsson U]] | ||
[[Category: Lecina | [[Category: Lecina D]] | ||
[[Category: Lepisto | [[Category: Lepisto M]] | ||
[[Category: Nilsson | [[Category: Nilsson E]] | ||
[[Category: Takahashi | [[Category: Takahashi R]] | ||
[[Category: Wissler | [[Category: Wissler L]] | ||
Revision as of 11:18, 22 March 2023
GR in complex with dexamethasoneGR in complex with dexamethasone
Structural highlights
DiseaseGCR_HUMAN Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:138040; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.[1] [2] [3] [4] [5] FunctionGCR_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.[6] Publication Abstract from PubMedSteroid receptor drugs have been available for more than half a century, but details of the ligand binding mechanism have remained elusive. We solved X-ray structures of the glucocorticoid and mineralocorticoid receptors to identify a conserved plasticity at the helix 6-7 region that extends the ligand binding pocket toward the receptor surface. Since none of the endogenous ligands exploit this region, we hypothesized that it constitutes an integral part of the binding event. Extensive all-atom unbiased ligand exit and entrance simulations corroborate a ligand binding pathway that gives the observed structural plasticity a key functional role. Kinetic measurements reveal that the receptor residence time correlates with structural rearrangements observed in both structures and simulations. Ultimately, our findings reveal why nature has conserved the capacity to open up this region, and highlight how differences in the details of the ligand entry process result in differential evolutionary constraints across the steroid receptors. Ligand Binding Mechanism in Steroid Receptors: From Conserved Plasticity to Differential Evolutionary Constraints.,Edman K, Hosseini A, Bjursell MK, Aagaard A, Wissler L, Gunnarsson A, Kaminski T, Kohler C, Backstrom S, Jensen TJ, Cavallin A, Karlsson U, Nilsson E, Lecina D, Takahashi R, Grebner C, Geschwindner S, Lepisto M, Hogner AC, Guallar V Structure. 2015 Dec 1;23(12):2280-90. doi: 10.1016/j.str.2015.09.012. Epub 2015, Oct 22. PMID:26602186[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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