4JFV

Crystal structure of a bacterial fucosidase with iminosugar inhibitor (2S,3S,4R,5S)-2-[N-(methylferrocene)]aminoethyl-5-methylpyrrolidine-3,4-diol

4JFV の概要

• エントリーDOI: 10.2210/pdb4jfv/pdb
• 関連するPDBエントリー: 2WVV 4J27 4J28 4JFS 4JFT 4JFU 4JFW
• 分子名称: alpha-L-fucosidase, SULFATE ION, IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: alpha-l-fucosidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 210996.99

構造登録者

Wright, D.W.,Davies, G.J. (登録日: 2013-02-28, 公開日: 2013-09-18, 最終更新日: 2023-09-20)

主引用文献

Hottin, A.,Wright, D.W.,Steenackers, A.,Delannoy, P.,Dubar, F.,Biot, C.,Davies, G.J.,Behr, J.B.
alpha-L-fucosidase inhibition by pyrrolidine-ferrocene hybrids: rationalization of ligand-binding properties by structural studies.
Chemistry, 19:9526-9533, 2013

PubMed Abstract: Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 μM.

PubMed: 23740878
DOI: 10.1002/chem.201301001

実験手法

X-RAY DIFFRACTION (1.88 Å)