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==Crystal structure of complexes of vitamin D receptor ligand binding domain with lithocholic acid derivatives== | |||
<StructureSection load='3w5t' size='340' side='right'caption='[[3w5t]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3w5t]] 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=3W5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W5T 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]] 2.29Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LHP:(3BETA,5BETA,9BETA)-3-(PROPANOYLOXY)CHOLAN-24-OIC+ACID'>LHP</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=3w5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w5t OCA], [https://pdbe.org/3w5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w5t RCSB], [https://www.ebi.ac.uk/pdbsum/3w5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w5t 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 == | |||
The secondary bile acid lithocholic acid (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that of the natural hormone 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Here, we have determined the crystal structures of the ligand binding domain of rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide of the coactivator MED1 (Mediator of RNA polymerase II transcription subunit 1) and four ligands, LCA, 3-keto LCA, LCA acetate, and LCA propionate, with the goal of elucidating their agonistic mechanism. LCA and its derivatives bind to the same ligand-binding pocket (LBP) of VDR-LBD that 1,25(OH)2D3 binds to, but in the opposite orientation; their A-ring is positioned at the top of the LBP, whereas their acyclic tail is located at the bottom of the LBP. However, most of the hydrophobic and hydrophilic interactions observed in the complex with 1,25(OH)2D3 are reproduced in the complexes with LCA and its derivatives. Additional interactions between VDR-LBD and the C-3 substituents of the A-ring are also observed in the complexes with LCA and its derivatives. These may result in the observed difference in the potency among the LCA-type ligands. | |||
Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives.,Masuno H, Ikura T, Morizono D, Orita I, Yamada S, Shimizu M, Ito N J Lipid Res. 2013 May 30. PMID:23723390<ref>PMID:23723390</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3w5t" 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: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Ikura T]] | |||
[[Category: Ito N]] | |||
[[Category: Masuno H]] | |||
Latest revision as of 15:50, 8 November 2023
Crystal structure of complexes of vitamin D receptor ligand binding domain with lithocholic acid derivativesCrystal structure of complexes of vitamin D receptor ligand binding domain with lithocholic acid derivatives
Structural highlights
FunctionVDR_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.[1] Publication Abstract from PubMedThe secondary bile acid lithocholic acid (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that of the natural hormone 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Here, we have determined the crystal structures of the ligand binding domain of rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide of the coactivator MED1 (Mediator of RNA polymerase II transcription subunit 1) and four ligands, LCA, 3-keto LCA, LCA acetate, and LCA propionate, with the goal of elucidating their agonistic mechanism. LCA and its derivatives bind to the same ligand-binding pocket (LBP) of VDR-LBD that 1,25(OH)2D3 binds to, but in the opposite orientation; their A-ring is positioned at the top of the LBP, whereas their acyclic tail is located at the bottom of the LBP. However, most of the hydrophobic and hydrophilic interactions observed in the complex with 1,25(OH)2D3 are reproduced in the complexes with LCA and its derivatives. Additional interactions between VDR-LBD and the C-3 substituents of the A-ring are also observed in the complexes with LCA and its derivatives. These may result in the observed difference in the potency among the LCA-type ligands. Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives.,Masuno H, Ikura T, Morizono D, Orita I, Yamada S, Shimizu M, Ito N J Lipid Res. 2013 May 30. PMID:23723390[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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