5OST

Beta-glucosidase from Thermoanaerobacterium xylolyticum GH116 in complex with Gluco-1H-imidazole

5OST の概要

• エントリーDOI: 10.2210/pdb5ost/pdb
• 分子名称: Glucosylceramidase, CALCIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Thermoanaerobacterium xylanolyticum (strain ATCC 49914 / DSM 7097 / LX-11)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 92708.26

構造登録者

Davies, G.J.,Offen, W.A. (登録日: 2017-08-18, 公開日: 2018-04-11, 最終更新日: 2024-01-17)

主引用文献

Schroder, S.P.,Wu, L.,Artola, M.,Hansen, T.,Offen, W.A.,Ferraz, M.J.,Li, K.Y.,Aerts, J.M.F.G.,van der Marel, G.A.,Codee, J.D.C.,Davies, G.J.,Overkleeft, H.S.
Gluco-1 H-imidazole: A New Class of Azole-Type beta-Glucosidase Inhibitor.
J. Am. Chem. Soc., 140:5045-5048, 2018

PubMed Abstract: Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and their ability to interact with catalytic acid residues in glucosidase active sites. We noted that no azole-type inhibitors described, to date, possess a protic nitrogen characteristic for 1 H-imidazoles. Here, we present gluco-1 H-imidazole, a gluco-azole bearing a 1 H-imidazole fused to a glucopyranose-configured cyclitol core, and three close analogues as new glucosidase inhibitors. All compounds inhibit human retaining β-glucosidase, GBA1, with the most potent ones inhibiting this enzyme (deficient in Gaucher disease) on a par with glucoimidazole. None inhibit glucosylceramide synthase, cytosolic β-glucosidase GBA2 or α-glucosidase GAA. Structural, physical and computational studies provide first insights into the binding mode of this conceptually new class of retaining β-glucosidase inhibitors.

PubMed: 29601200
DOI: 10.1021/jacs.8b02399

実験手法

X-RAY DIFFRACTION (2.1 Å)