View source for 3wwr


==Crystal structure of the human vitamin D receptor ligand binding domain complexed with 1-((((1S,2R,6R,Z)-2,6-dihydroxy-4-((E)-2-((1R,3aS,7aR)-1-((R)-6-hydroxy-6-methylheptan-2-yl)-7a-methylhexahydro-1H-inden-4(2H)-ylidene)ethylidene)-3-methylenecyclohexyl)oxy)methyl)cyclopropanecarbonitrile==
<StructureSection load='3wwr' size='340' side='right'caption='[[3wwr]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3wwr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WWR 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]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3AJ:1-({[(1R,2S,3R,5Z,7E,14BETA,17ALPHA)-1,3,25-TRIHYDROXY-9,10-SECOCHOLESTA-5,7,10-TRIEN-2-YL]OXY}METHYL)CYCLOPROPANECARBONITRILE'>3AJ</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=3wwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wwr OCA], [https://pdbe.org/3wwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wwr RCSB], [https://www.ebi.ac.uk/pdbsum/3wwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wwr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://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 ==
[https://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 ==
We synthesized and evaluated novel vitamin D3 derivatives with cyanoalkyl side chain at C-2 position on the basis of our previous research for 2alpha side chain which bears nitrogen atom-containing functional group. Through a study of X-ray co-crystal structures of human VDR and compound 3, we demonstrated that the 2alpha alkyl side chain in compound 3 shows a novel interaction in the complex of hVDR-LBD and ligand. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Synthesis and biological activities of vitamin D derivatives with cyanoalkyl side chain at C-2 position.,Saitoh H, Watanabe H, Kakuda S, Takimoto-Kamimura M, Takagi K, Takeuchi A, Takenouchi K J Steroid Biochem Mol Biol. 2014 Dec 10. pii: S0960-0760(14)00310-0. doi:, 10.1016/j.jsbmb.2014.12.004. PMID:25500068<ref>PMID:25500068</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3wwr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kakuda S]]
[[Category: Takimoto-Kamimura M]]