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==VDR ligand binding domain in complex with 2-Methylidene-26,27-dimethyl-19,24-dinor-1alpha,25-dihydroxyvitamin D3==
==VDR ligand binding domain in complex with 2-Methylidene-26,27-dimethyl-19,24-dinor-1alpha,25-dihydroxyvitamin D3==
<StructureSection load='3vrv' size='340' side='right' caption='[[3vrv]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='3vrv' size='340' side='right'caption='[[3vrv]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vrv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VRV FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vrv]] 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=3VRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VRV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSD:(1R,3R,7E,17BETA)-17-[(2R)-5-ETHYL-5-HYDROXYHEPTAN-2-YL]-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>YSD</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vru|3vru]], [[3vrt|3vrt]], [[3vrw|3vrw]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YSD:(1R,3R,7E,17BETA)-17-[(2R)-5-ETHYL-5-HYDROXYHEPTAN-2-YL]-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>YSD</scene></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=10116 Rattus norvegicus])</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=3vrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vrv OCA], [https://pdbe.org/3vrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vrv RCSB], [https://www.ebi.ac.uk/pdbsum/3vrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vrv ProSAT]</span></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=3vrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vrv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vrv RCSB], [http://www.ebi.ac.uk/pdbsum/3vrv PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref> 
[https://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Previously, we reported that 22S-butyl-25,26,27-trinor-1alpha,24-dihydroxyvitamin D(3)2 represents a new class of antagonist for the vitamin D receptor (VDR). The crystal structure of the ligand-binding domain (LBD) of VDR complexed with 2 showed the formation of a butyl pocket to accommodate the 22-butyl group and insufficient interactions between ligand 2 and the C-terminus of VDR. Here, we designed and synthesized new analogues 5a-c and evaluated their biological activities to probe whether agonistic activity is recovered when the analogue restores interactions with the C-terminus of VDR. Analogues 5a-c exhibited full agonistic activity in transactivation. Interestingly, 5c, which bears a 24-diethyl group, completely recovered agonistic activity, although 3c and 4c act as an antagonist and a weak agonist, respectively. The crystal structures of VDR-LBD complexed with 3a, 4a, 5a, and 5c were solved, and the results confirmed that butyl pocket formation in VDR strongly affects the agonistic or antagonistic behaviors of ligands.
 
Butyl pocket formation in the vitamin d receptor strongly affects the agonistic or antagonistic behavior of ligands.,Yoshimoto N, Sakamaki Y, Haeta M, Kato A, Inaba Y, Itoh T, Nakabayashi M, Ito N, Yamamoto K J Med Chem. 2012 May 10;55(9):4373-81. Epub 2012 Apr 27. PMID:22512505<ref>PMID:22512505</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Sandbox vdr|Sandbox vdr]]
*[[Sandbox vdr|Sandbox vdr]]
*[[Vitamin D receptor|Vitamin D receptor]]
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Inaba, Y]]
[[Category: Inaba Y]]
[[Category: Ito, N]]
[[Category: Ito N]]
[[Category: Itoh, T]]
[[Category: Itoh T]]
[[Category: Nakabayashi, M]]
[[Category: Nakabayashi M]]
[[Category: Yamamoto, K]]
[[Category: Yamamoto K]]
[[Category: Yoshimoto, N]]
[[Category: Yoshimoto N]]
[[Category: Co-factor]]
[[Category: Nuclear]]
[[Category: Nuclear hormone receptor]]
[[Category: Rxr]]
[[Category: Transcription]]
[[Category: Vdre]]
[[Category: Vitamin d3]]

Latest revision as of 08:41, 20 March 2024

VDR ligand binding domain in complex with 2-Methylidene-26,27-dimethyl-19,24-dinor-1alpha,25-dihydroxyvitamin D3

3vrv, resolution 1.90Å

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