1S19

Crystal structure of VDR ligand binding domain complexed to calcipotriol.

1S19 の概要

• エントリーDOI: 10.2210/pdb1s19/pdb
• 関連するPDBエントリー: 1DB1 1IE8 1IE9 1S0Z
• 分子名称: Vitamin D3 receptor, CALCIPOTRIOL (3 entities in total)
• 機能のキーワード: nuclear receptor, transcription regulation, alpha-helical sandwich, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P11473
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30217.95

構造登録者

Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,Moras, D. (登録日: 2004-01-06, 公開日: 2004-04-13, 最終更新日: 2024-02-14)

主引用文献

Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,Moras, D.
Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification.
J.Med.Chem., 47:1956-1961, 2004

PubMed Abstract: The plethora of actions of 1alpha,25(OH)(2)D(3) in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of these ligands. Here, we report the crystal structures of VDR ligand binding domain bound to two vitamin D agonists of therapeutical interest, calcipotriol and seocalcitol, which are characterized by their side chain modifications. These structures show the conservation of the VDR structure and the adaptation of the side chain anchored by hydroxyl moieties. The structure of VDR-calcipotriol helps us to understand the structural basis for for the switching of calcipotriol to a receptor antagonist by further side chain modification. The VDR-seocalcitol structure, in comparison with the structure of VDR-KH1060, a superagonist ligand closely related to seocalcitol, shows adaptation of the D ring and position of C-21 in order to adapt its more rigid side chain.

PubMed: 15055995
DOI: 10.1021/jm0310582

実験手法

X-RAY DIFFRACTION (2.1 Å)