3vtc: Difference between revisions
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==Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK3== | ==Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK3== | ||
<StructureSection load='3vtc' size='340' side='right' caption='[[3vtc]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='3vtc' size='340' side='right'caption='[[3vtc]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3vtc]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3vtc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VTC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TK3:(1R,3R,7E,17BETA)-17-{(2R,6R)-6-HYDROXY-7-[(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]HEPT-4-YN-2-YL}-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>TK3</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=TK3:(1R,3R,7E,17BETA)-17-{(2R,6R)-6-HYDROXY-7-[(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]HEPT-4-YN-2-YL}-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>TK3</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=3vtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vtc OCA], [https://pdbe.org/3vtc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vtc RCSB], [https://www.ebi.ac.uk/pdbsum/3vtc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vtc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3vtc" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ikura | [[Category: Rattus norvegicus]] | ||
[[Category: Ito | [[Category: Ikura T]] | ||
[[Category: Kudo | [[Category: Ito N]] | ||
[[Category: Makishima | [[Category: Kudo T]] | ||
[[Category: Nakabayashi | [[Category: Makishima M]] | ||
[[Category: Tokiwa | [[Category: Nakabayashi M]] | ||
[[Category: Yamada | [[Category: Tokiwa H]] | ||
[[Category: Yamada S]] | |||
Latest revision as of 15:37, 8 November 2023
Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK3Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK3
Structural highlights
FunctionVDR_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.[1] Publication Abstract from PubMedVitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1-4, 4b,a and 5a,b). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC50 10-9-10-8 M with 40-80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure-activity relationships of these compounds on the basis of their X-ray crystal structures. Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor.,Kudo T, Ishizawa M, Maekawa K, Nakabayashi M, Watarai Y, Uchida H, Tokiwa H, Ikura T, Ito N, Makishima M, Yamada S J Med Chem. 2014 May 7. PMID:24773565[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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