View source for 5ow7


==VDR complex==
<StructureSection load='5ow7' size='340' side='right'caption='[[5ow7]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ow7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OW7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYK:(3~{S})-3-[(1~{S},3~{a}~{S},4~{E},7~{a}~{S})-7~{a}-methyl-4-[(2~{Z})-2-[(5~{S})-2-methylidene-5-oxidanyl-cyclohexylidene]ethylidene]-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-1-yl]-3-oxidanyl-~{N}-propan-2-yl-butanamide'>AYK</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=5ow7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ow7 OCA], [https://pdbe.org/5ow7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ow7 RCSB], [https://www.ebi.ac.uk/pdbsum/5ow7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ow7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VDRA_DANRE VDRA_DANRE] 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. Plays a central role in calcium homeostasis.<ref>PMID:17218092</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic, suggesting its potential as a lead compound. In this study, side chain modified 20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1alpha-OH derivatives were synthesized and their metabolism and biological activities tested. 4, 13 and 23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1alpha-OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than calcitriol, indicating improved catabolic stability. While the parent analogs showed minimal VDR stimulating activity, their 1alpha-OH derivatives were potent VDR agonists. 4, 5, 14 and 24 significantly upregulated the expression of CYP24A1 at the mRNA level, consistent with their VDR activation abilities and indicating that 1alpha-hydroxylation is required to produce analogs with strong activity. These analogs have anti-inflammatory activities that are influenced by side chain composition and by 1alpha-hydroxylation. To understand their molecular interactions with the VDR, 20S(OH)D3, 4 and 33 were co-crystalized with the VDR ligand binding domain, which revealed subtle differences to the calcitriol-bound receptor. This study demonstrates the potential of the 20S(OH)D3 scaffold for the development of novel anti-inflammatory agents.

Investigation of 20S-hydroxyvitamin D3 analogs and their 1alpha-OH derivatives as potent vitamin D receptor agonists with anti-inflammatory activities.,Lin Z, Marepally SR, Goh ESY, Cheng CYS, Janjetovic Z, Kim TK, Miller DD, Postlethwaite AE, Slominski AT, Tuckey RC, Peluso-Iltis C, Rochel N, Li W Sci Rep. 2018 Jan 24;8(1):1478. doi: 10.1038/s41598-018-19183-7. PMID:29367669<ref>PMID:29367669</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ow7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Danio rerio]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li W]]
[[Category: Rochel N]]