2o4j
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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OverviewOverview
We have successfully prepared E- and Z- isomers of 17-20 dehydro analogs, of 2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D(3) (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 with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) 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. 2006 Dec 12;. PMID:17227670
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