View source for 3tkc

==Design, Synthesis, Evaluation and Structure of Vitamin D Analogues with Furan Side Chains==
<StructureSection load='3tkc' size='340' side='right' caption='[[3tkc]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tkc]] 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=3TKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TKC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMV:(1S,3R,5Z,7E,14BETA,17ALPHA,20S)-20-[5-(1-HYDROXY-1-METHYLETHYL)FURAN-2-YL]-9,10-SECOPREGNA-5,7,10-TRIENE-1,3-DIOL'>FMV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3a3z|3a3z]], [[3a40|3a40]]</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=3tkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tkc RCSB], [http://www.ebi.ac.uk/pdbsum/3tkc 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 ==
Based on the crystal structures of human vitamin D receptor (hVDR) bound to 1alpha,25-dihydroxy-vitamin D(3) (1,25 D) and superagonist ligands, we previously designed new superagonist ligands with a tetrahydrofuran ring at the side chain that optimize the aliphatic side-chain conformation through an entropy benefit. Following a similar strategy, four novel vitamin D analogues with aromatic furan side chains (3a, 3b, 4a, 4b) have now been developed. The triene system has been constructed by an efficient stereoselective intramolecular cyclization of an enol triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the resulting intermediate with an alkenyl boronic ester (CD-side chain, upper fragment). The furan side chains have been constructed by gold chemistry. These analogues exhibit significant pro-differentiation effects and transactivation potency. The crystal structure of 3a in a complex with the ligand-binding domain of hVDR revealed that the side-chain furanic ring adopts two conformations.

Design, synthesis, evaluation, and structure of vitamin D analogues with furan side chains.,Fraga R, Zacconi F, Sussman F, Ordonez-Moran P, Munoz A, Huet T, Molnar F, Moras D, Rochel N, Maestro M, Mourino A Chemistry. 2012 Jan 9;18(2):603-12. doi: 10.1002/chem.201102695. Epub 2011 Dec 8. PMID:22162241<ref>PMID:22162241</ref>

From MEDLINE&reg;/PubMed&reg;, 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: Huet, T]]
[[Category: Moras, D]]
[[Category: Rochel, N]]
[[Category: Alpha-helical sandwich]]
[[Category: Calcitriol]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Transcription]]