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3afr

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Revision as of 05:46, 5 August 2016

Crystal Structure of VDR-LBD/22S-Butyl-1a,24R-dihydroxyvitamin D3 complex

Structural highlights

3afr is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2zxm, 2zxn
Gene:	VDR, NR1I1 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] [MED1_XENTR] 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 (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vanhooke JL, Tadi BP, Benning MM, Plum LA, DeLuca HF. New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 with conformationally restricted side chains: evaluation of biological activity and structural determination of VDR-bound conformations. Arch Biochem Biophys. 2007 Apr 15;460(2):161-5. Epub 2006 Dec 12. PMID:17227670 doi:10.1016/j.abb.2006.11.029
↑ Inaba Y, Nakabayashi M, Itoh T, Yoshimoto N, Ikura T, Ito N, Shimizu M, Yamamoto K. 22S-butyl-1alpha,24R-dihydroxyvitamin D3: recovery of vitamin D receptor agonistic activity. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):146-50. Epub 2010 Mar 6. PMID:20211257 doi:10.1016/j.jsbmb.2010.02.033

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3afr"

@@ Line 1: / Line 1: @@
 ==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 [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AFR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3afr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AFR FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zxm|2zxm]], [[2zxn|2zxn]]</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='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 Buffalo rat])</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=3afr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3afr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3afr RCSB], [http://www.ebi.ac.uk/pdbsum/3afr PDBsum]</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=3afr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3afr OCA], [http://pdbe.org/3afr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3afr RCSB], [http://www.ebi.ac.uk/pdbsum/3afr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3afr ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3afr" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Rattus norvegicus]]
+[[Category: Buffalo rat]]
 [[Category: Ikura, T]]
 [[Category: Inaba, Y]]

3afr

From Proteopedia

Revision as of 05:46, 5 August 2016

Crystal Structure of VDR-LBD/22S-Butyl-1a,24R-dihydroxyvitamin D3 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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