2o4j: Difference between revisions

Revision as of 10:18, 4 May 2008

Crystal Structure of Rat Vitamin D Receptor Ligand Binding Domain Complexed with VitIII 17-20Z and the NR2 Box of DRIP 205

OverviewOverview

We have successfully prepared E- and Z- isomers of 17-20 dehydro analogs of 2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD). Both isomers bind to the recombinant rat vitamin D receptor (VDR) with high affinity. The Z-isomer (Vit-III 17-20Z) displays activity in vivo and in vitro that is similar to 2MD. The in vitro activity of the E-isomer (Vit-III 17-20E) is comparable to the natural hormone, though in vivo this analog is significantly less calcemic. Crystal structures of the rat VDR ligand binding domain complexed with the analogs demonstrate that the Vit-III 17-20Z analog is oriented almost identically to 2MD, with only minor differences induced by the planar configuration around the C17-C20 double bond. The Vit-III 17-20E analog is oriented in a conformation distinct from both 2MD and the natural hormone. The structural comparisons suggest that the position of C21 in the ligand binding site may be an important determinant of biological activity.

About this StructureAbout this Structure

2O4J is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

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., Vanhooke JL, Tadi BP, Benning MM, Plum LA, DeLuca HF, Arch Biochem Biophys. 2007 Apr 15;460(2):161-5. Epub 2006 Dec 12. PMID:17227670 Page seeded by OCA on Sun May 4 10:18:59 2008

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OCA

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 [[Image:2o4j.gif|left|200px]]
- {{Structure
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-|GENE= Vdr, Nr1i1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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-|DOMAIN=
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o4j OCA], [http://www.ebi.ac.uk/pdbsum/2o4j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2o4j RCSB]</span>
-}}
 '''Crystal Structure of Rat Vitamin D Receptor Ligand Binding Domain Complexed with VitIII 17-20Z and the NR2 Box of DRIP 205'''
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 [[Category: DeLuca, H F.]]
 [[Category: Vanhooke, J L.]]
-[[Category: nuclear receptor-ligand complex]]
+[[Category: Nuclear receptor-ligand complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 10:18:59 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:12:33 2008''