5e7v

From Proteopedia

(Difference between revisions)

Current revision

Potent Vitamin D Receptor Agonist

Structural highlights

5e7v is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VDRA_DANRE 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. Plays a central role in calcium homeostasis.^[1]

Publication Abstract from PubMed

The vitamin D nuclear receptor (VDR) is a potential target for cancer therapy. It is expressed in many tumors and its ligand shows anticancer actions. To combine these properties with the application of boron neutron capture therapy (BNCT), we design and synthesize a potent VDR agonist based on the skeleton of the hormone 1alpha,25-dihydroxyvitamin D3 (1,25D) and an o-carborane (dicarba-o-closo-1,2-dodecaborane) at the end of its side chain. The present ligand is the first secosteroidal analog with the carborane unit that efficiently binds to VDR and functions as an agonist with 1,25D-like potency in transcriptional assay on vitamin D target genes. Moreover it exhibits similar antiproliferative and pro-differentiating activities but is significantly less hypercalcemic than 1,25D. The crystal structure of its complex with VDR ligand binding domain reveals its binding mechanism involving boron-mediated dihydrogen bonds that mimic vitamin D hydroxyl interactions. In addition to the therapeutic interest, this study establishes the basis for the design of new unconventional vitamin D analogs containing carborane moieties for specific molecular recognition, and drug research and development.

Carborane-based design of a potent vitamin D receptor agonist.,Otero R, Seoane S, Sigueiro R, Belorusova AY, Maestro MA, Perez-Fernandez R, Rochel N, Mourino A Chem Sci. 2016 Feb 1;7(2):1033-1037. doi: 10.1039/c5sc03084f. Epub 2015 Oct 27. PMID:28808527^[2]

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

References

↑ Ciesielski F, Rochel N, Moras D. Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42. Epub 2007 Jan 10. PMID:17218092 doi:http://dx.doi.org/10.1016/j.jsbmb.2006.12.003
↑ Otero R, Seoane S, Sigueiro R, Belorusova AY, Maestro MA, Perez-Fernandez R, Rochel N, Mourino A. Carborane-based design of a potent vitamin D receptor agonist. Chem Sci. 2016 Feb 1;7(2):1033-1037. doi: 10.1039/c5sc03084f. Epub 2015 Oct 27. PMID:28808527 doi:http://dx.doi.org/10.1039/c5sc03084f

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e7v"

@@ Line 1: / Line 1: @@
 ==Potent Vitamin D Receptor Agonist==
-<StructureSection load='5e7v' size='340' side='right' caption='[[5e7v]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5e7v' size='340' side='right'caption='[[5e7v]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e7v]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E7V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E7V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e7v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E7V FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M7E:1-ALPHA-HYDROXY-27-NOR-25-O-CARBONYL-VITAMIN+D3'>M7E</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]] 2.4&#8491;</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=5e7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e7v OCA], [http://pdbe.org/5e7v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e7v RCSB], [http://www.ebi.ac.uk/pdbsum/5e7v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e7v ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7E:1-ALPHA-HYDROXY-27-NOR-25-O-CARBONYL-VITAMIN+D3'>M7E</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=5e7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e7v OCA], [https://pdbe.org/5e7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e7v RCSB], [https://www.ebi.ac.uk/pdbsum/5e7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e7v ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/VDRA_DANRE VDRA_DANRE]] 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. Plays a central role in calcium homeostasis.<ref>PMID:17218092</ref>
+[https://www.uniprot.org/uniprot/VDRA_DANRE VDRA_DANRE] 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. Plays a central role in calcium homeostasis.<ref>PMID:17218092</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 ==See Also==
-*[[Vitamin D receptor|Vitamin D receptor]]
+*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Belorusova, A Y]]
+[[Category: Danio rerio]]
-[[Category: Maestro, M A]]
+[[Category: Homo sapiens]]
-[[Category: Mourino, A]]
+[[Category: Large Structures]]
-[[Category: Otero, R]]
+[[Category: Belorusova AY]]
-[[Category: Perez-Fernandez, R]]
+[[Category: Maestro MA]]
-[[Category: Rochel, N]]
+[[Category: Mourino A]]
-[[Category: Seoane, S]]
+[[Category: Otero R]]
-[[Category: Sigueiro, R]]
+[[Category: Perez-Fernandez R]]
-[[Category: Ligand binding domain]]
+[[Category: Rochel N]]
-[[Category: Transcription]]
+[[Category: Seoane S]]
-[[Category: Vdr]]
+[[Category: Sigueiro R]]
-[[Category: Vitamin d nuclear receptor]]

5e7v

From Proteopedia

Current revision

Potent Vitamin D Receptor Agonist

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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