View source for 5zwh


==Covalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having an ene-ynone group via conjugate addition reaction==
<StructureSection load='5zwh' size='340' side='right'caption='[[5zwh]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zwh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZWH 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]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9KX:(2S,4E,6E)-2-[(1R,3R,7E,17beta)-1,3-dihydroxy-2-methylidene-9,10-secoestra-5,7-dien-17-yl]octa-4,6-dien-3-one'>9KX</scene>, <scene name='pdbligand=9N9:(~{E},2~{S})-2-[(1~{R},3~{a}~{S},4~{E},7~{a}~{R})-7~{a}-methyl-4-[2-[(3~{R},5~{R})-4-methylidene-3,5-bis(oxidanyl)cyclohexylidene]ethylidene]-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-1-yl]oct-6-en-4-yn-3-one'>9N9</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=5zwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zwh OCA], [https://pdbe.org/5zwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zwh RCSB], [https://www.ebi.ac.uk/pdbsum/5zwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zwh 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We designed and synthesized vitamin D analogues with an electrophile as covalent modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an electrophilic enone group at the side chain for conjugate addition to His301 or His393 in the VDR. All compounds showed specific VDR-binding potency and agonistic activity. Covalent bond formations of 1-4 with the ligand-binding domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry. All compounds were shown to covalently bind to the VDR-LBD, and the abundance of VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time. Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301 in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent bond with VDR-LBD.

Identification of the Histidine Residue in Vitamin D Receptor That Covalently Binds to Electrophilic Ligands.,Yoshizawa M, Itoh T, Hori T, Kato A, Anami Y, Yoshimoto N, Yamamoto K J Med Chem. 2018 Jul 11. doi: 10.1021/acs.jmedchem.8b00774. PMID:29936834<ref>PMID:29936834</ref>

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

==See Also==
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Anami Y]]
[[Category: Itoh T]]
[[Category: Kato A]]
[[Category: Yamamoto K]]
[[Category: Yoshimoto N]]
[[Category: Yoshizawa M]]