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3vtb

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Revision as of 14:24, 5 August 2016

Crystal structure of rat vitamin D receptor bound to a partial agonist 25-adamantyl-23-yne-19-norvitammin D ADTK1

Structural highlights

3vtb 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:	2zlc, 3vtc, 3vtd
Gene:	Nr1i1, Vdr (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]

Publication Abstract from PubMed

Vitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1-4, 4b,a and 5a,b). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC50 10-9-10-8 M with 40-80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure-activity relationships of these compounds on the basis of their X-ray crystal structures.

Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor.,Kudo T, Ishizawa M, Maekawa K, Nakabayashi M, Watarai Y, Uchida H, Tokiwa H, Ikura T, Ito N, Makishima M, Yamada S J Med Chem. 2014 May 7. PMID:24773565^[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
↑ Kudo T, Ishizawa M, Maekawa K, Nakabayashi M, Watarai Y, Uchida H, Tokiwa H, Ikura T, Ito N, Makishima M, Yamada S. Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor. J Med Chem. 2014 May 7. PMID:24773565 doi:http://dx.doi.org/10.1021/jm401989c

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of rat vitamin D receptor bound to a partial agonist 25-adamantyl-23-yne-19-norvitammin D ADTK1==
 <StructureSection load='3vtb' size='340' side='right' caption='[[3vtb]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zlc|2zlc]], [[3vtc|3vtc]], [[3vtd|3vtd]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nr1i1, Vdr ([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=3vtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vtb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vtb RCSB], [http://www.ebi.ac.uk/pdbsum/3vtb 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=3vtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vtb OCA], [http://pdbe.org/3vtb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vtb RCSB], [http://www.ebi.ac.uk/pdbsum/3vtb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vtb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3vtb" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3vtb

From Proteopedia

Revision as of 14:24, 5 August 2016

Crystal structure of rat vitamin D receptor bound to a partial agonist 25-adamantyl-23-yne-19-norvitammin D ADTK1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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