3VJS

Vitamin D receptor complex with a carborane compound

3VJS の概要

• エントリーDOI: 10.2210/pdb3vjs/pdb
• 関連するPDBエントリー: 3VJT
• 分子名称: Vitamin D3 receptor, peptide from Mediator of RNA polymerase II transcription subunit 1, 1-(2-[(S)-2,4-Dihydroxybutoxy]ethyl)-12-(5-ethyl-5-hydroxyheptyl)-1,12-dicarba-closo-dodecaborane, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, synthetic agonist, carborane, transcription
• 由来する生物種: Rattus norvegicus (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: 32584.56

構造登録者

Fujii, S.,Masuno, M.,Kagechika, H.,Nakabayashi, M.,Ito, N. (登録日: 2011-10-31, 公開日: 2012-02-08, 最終更新日: 2023-11-08)

主引用文献

Fujii, S.,Masuno, H.,Taoda, Y.,Kano, A.,Wongmayura, A.,Nakabayashi, M.,Ito, N.,Shimizu, M.,Kawachi, E.,Hirano, T.,Endo, Y.,Tanatani, A.,Kagechika, H.
Boron Cluster-based Development of Potent Nonsecosteroidal Vitamin D Receptor Ligands: Direct Observation of Hydrophobic Interaction between Protein Surface and Carborane
J.Am.Chem.Soc., 133:20933-20941, 2011

PubMed Abstract: We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo-dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical stability and a characteristically hydrophobic B-H surface). This carborane-based VDR ligand exhibited moderate vitamin D activity, comparable to that of the natural hormone, despite its simple and flexible structure. X-ray structure analysis provided direct evidence that the carborane cage binds to the hydrophobic surface of the ligand-binding pocket of the receptor, promoting transition to the active conformation. These results indicate that the spherical B-H surface of carborane can function efficiently as a hydrophobic anchor in binding to the receptor surface, thereby allowing induced fitting of the three essential hydroxyl groups on the alkyl chains to the appropriate positions for interaction with the VDR binding site, despite the entropic disadvantage of the flexible structure. We suggest that carborane structure is a promising option in the design of novel drug candidates.

PubMed: 22066785
DOI: 10.1021/ja208797n

実験手法

X-RAY DIFFRACTION (1.93 Å)