View source for 2ham


==Crystal structure of VDR LBD complexed to 2alpha-propyl-calcitriol==
<StructureSection load='2ham' size='340' side='right'caption='[[2ham]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ham]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HAM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C33:2ALPHA-PROPYL-1ALPHA,25-DIHYDROXYVITAMIN+D3'>C33</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1db1|1db1]], [[1s0z|1s0z]], [[1s19|1s19]], [[1ie8|1ie8]], [[1ie9|1ie9]], [[1txi|1txi]], [[2har|2har]], [[2has|2has]], [[2hb7|2hb7]], [[2hb8|2hb8]]</div></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=2ham FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ham OCA], [https://pdbe.org/2ham PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ham RCSB], [https://www.ebi.ac.uk/pdbsum/2ham PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ham 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>  
== 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/ha/2ham_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=2ham ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures.

Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues.,Hourai S, Fujishima T, Kittaka A, Suhara Y, Takayama H, Rochel N, Moras D J Med Chem. 2006 Aug 24;49(17):5199-205. PMID:16913708<ref>PMID:16913708</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ham" 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: Human]]
[[Category: Large Structures]]
[[Category: Hourai, S]]
[[Category: Moras, D]]
[[Category: Rochel, N]]
[[Category: Alpha-helical sandwich]]
[[Category: Gene regulation]]