5b5b
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of VDR-LBD complexed with 2-methylidene-26,27-diphenyl-19-nor-1,25-dihydroxyvitamin D3== | |
| + | <StructureSection load='5b5b' size='340' side='right' caption='[[5b5b]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5b5b]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B5B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKX:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-7A-METHYL-1-[(2R)-6-OXIDANYL-7-PHENYL-6-(PHENYLMETHYL)HEPTAN-2-YL]-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>AKX</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=5b5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b5b OCA], [http://pdbe.org/5b5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b5b RCSB], [http://www.ebi.ac.uk/pdbsum/5b5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b5b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:17227670</ref> [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | To develop strong vitamin D receptor (VDR) antagonists and reveal their antagonistic mechanism, we designed and synthesized vitamin D analogues with bulky side chains based on the "active antagonist" concept in which antagonist prevents helix 12 (H12) folding. Of the synthesized analogues, compounds 3a and 3b showed strong antagonistic activity. Dynamic hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) and static X-ray crystal structure analyses indicated that compound 3a stabilizes H11-H12 but displaces H6-H7 so that 3a is a novel rather than "active" or "passive" type of antagonist. We classified 3a as a third type of antagonist and called it "H11-H12 stabilization antagonist". HDX-MS analysis indicated that antagonist 3b is an "active" antagonist. To date there are no reports relating to nuclear receptor antagonist that strongly stabilizes H12. In this study, we found first VDR antagonist that stabilizes H12 and we showed that antagonistic mechanism is diverse depending on each antagonist structure. Additionally, HDX-MS was proven to be very useful for investigations of protein structure alterations resulting from ligand binding. | ||
| - | + | Helix12-Stabilization Antagonist of Vitamin D Receptor.,Kato A, Itoh T, Anami Y, Egawa D, Yamamoto K Bioconjug Chem. 2016 Jun 27. PMID:27294600<ref>PMID:27294600</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5b5b" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Itoh, T]] | [[Category: Itoh, T]] | ||
[[Category: Kato, A]] | [[Category: Kato, A]] | ||
| + | [[Category: Yamamoto, K]] | ||
| + | [[Category: Antagonist]] | ||
| + | [[Category: Co-factor]] | ||
| + | [[Category: Rxr]] | ||
| + | [[Category: Transcription]] | ||
| + | [[Category: Vdr]] | ||
| + | [[Category: Vdre]] | ||
| + | [[Category: Vitamin d3]] | ||
Revision as of 10:17, 13 July 2016
Crystal structure of VDR-LBD complexed with 2-methylidene-26,27-diphenyl-19-nor-1,25-dihydroxyvitamin D3
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Categories: Itoh, T | Kato, A | Yamamoto, K | Antagonist | Co-factor | Rxr | Transcription | Vdr | Vdre | Vitamin d3
