View source for 3afr


==Crystal Structure of VDR-LBD/22S-Butyl-1a,24R-dihydroxyvitamin D3 complex==
<StructureSection load='3afr' size='340' side='right'caption='[[3afr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3afr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AFR 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ICJ:(1R,3S,5Z)-5-[(2E)-2-{(1R,3AS,7AR)-1-[(1R,2S,4R)-2-BUTYL-4-HYDROXY-1,5-DIMETHYLHEXYL]-7A-METHYLOCTAHYDRO-4H-INDEN-4-YLIDENE}ETHYLIDENE]-4-METHYLIDENECYCLOHEXANE-1,3-DIOL'>ICJ</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=3afr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3afr OCA], [https://pdbe.org/3afr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3afr RCSB], [https://www.ebi.ac.uk/pdbsum/3afr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3afr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VDR_RAT VDR_RAT] 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:17227670</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/af/3afr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3afr ConSurf].
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== Publication Abstract from PubMed ==
We recently reported that 22S-butyl-1alpha,24R-dihydroxyvitamin D(3)3 recovers the agonistic activity for vitamin D receptor (VDR), although its 25,26,27-trinor analog 2 is a potent VDR antagonist. To investigate the structural features involved in the recovery of agonism, we crystallized the ternary complex of VDR-ligand-binding domain, ligand 3 and coactivator peptide, and conducted X-ray crystallographic analysis of the complex. Compared with the complex with 2, the complex with 3 recovered the following structural features: a pincer-type hydrogen bond between the 24-hydroxyl group and VDR, the conformation of Leu305, the positioning of His301 and His393, the stability of the complex, and intimate hydrophobic interactions between the ligand and helix 12. In addition, we evaluated the potency of both compounds for recruiting RXR and coactivator. The results indicate that the complex with 3 generates a suitable surface for coactivator recruitment. These studies suggest that the action of 2 as an antagonist is caused by the generation of a surface not suitable for coactivator recruitment due to the lack of hydrophobic interactions with helix 12 as well as insufficient hydrogen bond formation between the 24-hydroxyl group and VDR. We concluded that the action of 3 as an agonist is based on the elimination of these structural defects in the complex with 2.

22S-butyl-1alpha,24R-dihydroxyvitamin D3: recovery of vitamin D receptor agonistic activity.,Inaba Y, Nakabayashi M, Itoh T, Yoshimoto N, Ikura T, Ito N, Shimizu M, Yamamoto K J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):146-50. Epub 2010 Mar 6. PMID:20211257<ref>PMID:20211257</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3afr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sandbox vdr|Sandbox vdr]]
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Xenopus tropicalis]]
[[Category: Ikura T]]
[[Category: Inaba Y]]
[[Category: Ito N]]
[[Category: Itoh T]]
[[Category: Nakabayashi M]]
[[Category: Yamamoto K]]