5O0S

Crystal structure of txGH116 (beta-glucosidase from Thermoanaerobacterium xylolyticum) in complex with unreacted beta Cyclophellitol Cyclosulfate probe ME711

5O0S の概要

• エントリーDOI: 10.2210/pdb5o0s/pdb
• 関連するPDBエントリー: 5NPF
• 分子名称: Glucosylceramidase, 1,2-ETHANEDIOL, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Thermoanaerobacterium xylanolyticum LX-11
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 91221.52

構造登録者

Wu, L.,Offen, W.A.,Breen, I.Z.,Davies, G.J. (登録日: 2017-05-16, 公開日: 2017-08-09, 最終更新日: 2024-01-17)

主引用文献

Artola, M.,Wu, L.,Ferraz, M.J.,Kuo, C.L.,Raich, L.,Breen, I.Z.,Offen, W.A.,Codee, J.D.C.,van der Marel, G.A.,Rovira, C.,Aerts, J.M.F.G.,Davies, G.J.,Overkleeft, H.S.
1,6-Cyclophellitol Cyclosulfates: A New Class of Irreversible Glycosidase Inhibitor.
ACS Cent Sci, 3:784-793, 2017

PubMed Abstract: The essential biological roles played by glycosidases, coupled to the diverse therapeutic benefits of pharmacologically targeting these enzymes, provide considerable motivation for the development of new inhibitor classes. Cyclophellitol epoxides and aziridines are recently established covalent glycosidase inactivators. Inspired by the application of cyclic sulfates as electrophilic equivalents of epoxides in organic synthesis, we sought to test whether cyclophellitol cyclosulfates would similarly act as irreversible glycosidase inhibitors. Here we present the synthesis, conformational analysis, and application of novel 1,6-cyclophellitol cyclosulfates. We show that 1,6--cyclophellitol cyclosulfate (α-cyclosulfate) is a rapidly reacting α-glucosidase inhibitor whose C chair conformation matches that adopted by α-glucosidase Michaelis complexes. The 1,6-cyclophellitol cyclosulfate (β-cyclosulfate) reacts more slowly, likely reflecting its conformational restrictions. Selective glycosidase inhibitors are invaluable as mechanistic probes and therapeutic agents, and we propose cyclophellitol cyclosulfates as a valuable new class of carbohydrate mimetics for application in these directions.

PubMed: 28776021
DOI: 10.1021/acscentsci.7b00214

実験手法

X-RAY DIFFRACTION (1.16 Å)