2HAR

Crystal structure of VDR LBD in complex with 2 alpha-(3-hydroxy-1-propoxy) calcitriol

2HAR の概要

• エントリーDOI: 10.2210/pdb2har/pdb
• 関連するPDBエントリー: 1DB1 1IE8 1IE9 1S0Z 1S19 1TXI 2HAM 2HAS 2HB7 2HB8
• 分子名称: Vitamin D3 receptor, 2ALPHA-(3-HYDROXYPROPOXY)-1ALPHA,25-DIHYDROXYVITAMIN D3 (3 entities in total)
• 機能のキーワード: 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: 30296.06

構造登録者

Hourai, S.,Rochel, N.,Moras, D. (登録日: 2006-06-13, 公開日: 2006-08-29, 最終更新日: 2023-10-25)

主引用文献

Hourai, S.,Fujishima, T.,Kittaka, A.,Suhara, Y.,Takayama, H.,Rochel, N.,Moras, D.
Probing a Water Channel near the A-Ring of Receptor-Bound 1alpha,25-Dihydroxyvitamin D3 with Selected 2alpha-Substituted Analogues
J.Med.Chem., 49:5199-5205, 2006

PubMed Abstract: The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures.

PubMed: 16913708
DOI: 10.1021/jm0604070

実験手法

X-RAY DIFFRACTION (1.9 Å)