4PEE

Crystal structure of a bacterial fucosidase with inhibitor 1-phenyl-4-[(2S,3S,4R,5S)-3,4-dihydroxy-5-methylpyrrolidin-2-yl]triazole

4PEE の概要

• エントリーDOI: 10.2210/pdb4pee/pdb
• 分子名称: Alpha-L-fucosidase, SULFATE ION, IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Bacteroides thetaiotaomicron
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 209065.38

構造登録者

Wright, D.W.,Davies, G.J.,Behr, J.B. (登録日: 2014-04-23, 公開日: 2014-07-09, 最終更新日: 2023-12-20)

主引用文献

Hottin, A.,Wright, D.W.,Davies, G.J.,Behr, J.B.
Exploiting the Hydrophobic Terrain in Fucosidases with Aryl-Substituted Pyrrolidine Iminosugars.
Chembiochem, 16:277-283, 2015

PubMed Abstract: Fucosidase inhibition shows potential in numerous therapeutic contexts. Substitution of fucose-like iminosugars with hydrophobic "aglycons" yields significant improvements in potency of fucosidase inhibition. Here we have prepared three new 2-aryl-3,4-dihydroxy-5-methylpyrrolidines featuring phenyl substituents in variable orientations with respect to the iminocyclitol core and at various distances from it to explore the key binding interactions that stabilise the enzyme-inhibitor complex. The presence of a triazole linker in one structure resulted in nanomolar inhibition of the fucosidase from bovine kidney (Ki =4.8 nM), thus giving rise to one of the most potent pyrrolidine-type inhibitors of this enzyme known to date.

PubMed: 25427942
DOI: 10.1002/cbic.201402509

実験手法

X-RAY DIFFRACTION (1.95 Å)