3p8x: Difference between revisions
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==Synthesis, Structure, and Biological Activity of des-Side Chain Analogues of 1alpha,25-Dihydroxyvitamin D3 with Substituents at C-18== | |||
<StructureSection load='3p8x' size='340' side='right' caption='[[3p8x]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3p8x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P8X FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZYD:(1R,3S,5Z)-5-{(2E)-2-[(3AR,7AS)-7A-(7-HYDROXY-7-METHYLOCTYL)OCTAHYDRO-4H-INDEN-4-YLIDENE]ETHYLIDENE}-4-METHYLIDENECYCLOHEXANE-1,3-DIOL'>ZYD</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1db1|1db1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3p8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p8x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p8x RCSB], [http://www.ebi.ac.uk/pdbsum/3p8x PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] 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:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
An improved synthetic route to 1alpha,25-dihydroxyvitamin D(3) des-side chain analogues 2 a and 2 b with substituents at C18 is reported, along with their biological activity. These analogues display significant antiproliferative effects toward MCF-7 breast cancer cells and prodifferentiation activity toward SW480-ADH colon cancer cells; they are also characterized by a greatly decreased calcemic profile. The crystal structure of the human vitamin D receptor (hVDR) complexed to one of these analogues, 20(17-->18)-abeo-1alpha,25-dihydroxy-22-homo-21-norvitamin D(3) (2 a) reveals that the side chain introduced at position C18 adopts the same orientation in the ligand binding pocket as the side chain of 1alpha,25-dihydroxyvitamin D(3). | |||
Synthesis, structure, and biological activity of des-side chain analogues of 1alpha,25-dihydroxyvitamin D3 with substituents at C18.,Verlinden L, Verstuyf A, Eelen G, Bouillon R, Ordonez-Moran P, Larriba MJ, Munoz A, Rochel N, Sato Y, Moras D, Maestro M, Seoane S, Dominguez F, Eduardo-Canosa S, Nicoletti D, Moman E, Mourino A ChemMedChem. 2011 May 2;6(5):788-93. doi: 10.1002/cmdc.201100021. Epub, 2011 Mar 29. PMID:21520419<ref>PMID:21520419</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
[[ | *[[Sandbox vdr|Sandbox vdr]] | ||
*[[Vitamin D receptor|Vitamin D receptor]] | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Moras, D | [[Category: Moras, D]] | ||
[[Category: Rochel, N | [[Category: Rochel, N]] | ||
[[Category: Sato, Y | [[Category: Sato, Y]] | ||
[[Category: Helices sandwich]] | [[Category: Helices sandwich]] | ||
[[Category: Transcription regulation]] | [[Category: Transcription regulation]] | ||
[[Category: Transcription regulator]] | [[Category: Transcription regulator]] | ||
[[Category: Vitamin d]] | [[Category: Vitamin d]] | ||
