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==Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK4== | |||
<StructureSection load='3vtd' size='340' side='right' caption='[[3vtd]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3vtd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VTD OCA]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TKD:(1R,3R,7E,17BETA)-17-{(2R,6S)-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'>TKD</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zlc|2zlc]], [[3vtb|3vtb]], [[3vtc|3vtc]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nr1i1, Vdr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vtd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vtd RCSB], [http://www.ebi.ac.uk/pdbsum/3vtd PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Vitamin 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<ref>PMID:24773565</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
<references | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Buffalo rat]] | |||
[[Category: Ikura, T.]] | [[Category: Ikura, T.]] | ||
[[Category: Ito, N.]] | [[Category: Ito, N.]] | ||
Revision as of 09:37, 14 May 2014
Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK4Crystal structure of rat vitamin D receptor bound to a partial agonist 26-adamantyl-23-yne-19-norvitammin D ADTK4
Structural highlights
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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