2O4R

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

Summary for 2O4R

• Entry DOI: 10.2210/pdb2o4r/pdb
• Related: 1RJK 1RK3 2O4J
• Descriptor: Vitamin D3 receptor, Peroxisome proliferator-activated receptor-binding protein, (1R,3R,7E,17E)-17-(5-hydroxy-1,5-dimethylhexylidene)-2-methylene-9,10-secoestra-5,7-diene-1,3-diol, ... (4 entities in total)
• Functional Keywords: nuclear receptor-ligand complex, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Nucleus: P13053 Q15648
• Total number of polymer chains: 2
• Total formula weight: 34969.25

Authors

Vanhooke, J.L.,Benning, M.M.,DeLuca, H.F. (deposition date: 2006-12-04, release date: 2007-01-30, Last modification date: 2023-08-30)

Primary citation

Vanhooke, J.L.,Tadi, B.P.,Benning, M.M.,Plum, L.A.,Deluca, H.F.
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.
Arch.Biochem.Biophys., 460:161-165, 2007

PubMed Abstract: 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.

PubMed: 17227670
DOI: 10.1016/j.abb.2006.11.029

Experimental method

X-RAY DIFFRACTION (1.98 Å)