2O4J

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

2O4J の概要

• エントリーDOI: 10.2210/pdb2o4j/pdb
• 関連するPDBエントリー: 1RJK 1RK3 2O4R
• 分子名称: Vitamin D3 receptor, Peroxisome proliferator-activated receptor-binding protein, (1R,3R,7E,17Z)-17-(5-hydroxy-1,5-dimethylhexylidene)-2-methylene-9,10-secoestra-5,7-diene-1,3-diol, ... (4 entities in total)
• 機能のキーワード: nuclear receptor-ligand complex, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Nucleus: P13053 Q15648
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34969.25

構造登録者

Vanhooke, J.L.,Benning, M.M.,DeLuca, H.F. (登録日: 2006-12-04, 公開日: 2007-01-30, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.74 Å)