4ynk
From Proteopedia
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| - | ''' | + | ==Crystal structure of vitamin D receptor ligand binding domain complexed with a 19-norvitamin D compound== |
| + | <StructureSection load='4ynk' size='340' side='right' caption='[[4ynk]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ynk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YNK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YNK FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YW2:(1R,3R,7E,17BETA)-17-{(5S)-5-HYDROXY-5-[(3R,5R,7R)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]PENTA-1,3-DIYN-1-YL}-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>YW2</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=4ynk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ynk OCA], [http://pdbe.org/4ynk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ynk RCSB], [http://www.ebi.ac.uk/pdbsum/4ynk PDBsum]</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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D receptor (VDR) to modulate its activities. The analogue 5b binds to the VDR (7% of the natural hormone) and shows significant partial agonistic activity in transactivation assay. Compound 5b showed considerable selectivity in VDR target genes expressions in vitro, it was taken up by target cells 2-3 times more readily, and its lifetime was three times longer than the natural hormone. The X-ray crystal structure of 5b in complex with VDR reveals that the ligand binds similarly to the natural hormone, but the diyne moiety is slightly bent (angles around the diyne 5 degrees to 8 degrees ) with respect to the original diyne vitamin D compound 6 in VDR (<1 degrees ) due to steric hindrance with helix 12. | ||
| - | + | Synthesis, Biological Activities, and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds.,Watarai Y, Ishizawa M, Ikura T, Zacconi FC, Uno S, Ito N, Mourino A, Tokiwa H, Makishima M, Yamada S J Med Chem. 2015 Dec 24;58(24):9510-21. doi: 10.1021/acs.jmedchem.5b00792. Epub, 2015 Dec 15. PMID:26613420<ref>PMID:26613420</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 4ynk" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Ikura, T]] | ||
[[Category: Ito, N]] | [[Category: Ito, N]] | ||
[[Category: Watarai, Y]] | [[Category: Watarai, Y]] | ||
| - | [[Category: | + | [[Category: Hormone receptor]] |
| + | [[Category: Transcription]] | ||
Revision as of 16:59, 20 January 2016
Crystal structure of vitamin D receptor ligand binding domain complexed with a 19-norvitamin D compound
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