5I23

Crystal Structure of Agd31B, alpha-transglucosylase in Glycoside Hydrolase Family 31, in complex with Cyclophellitol Aziridine probe CF022

5I23 の概要

• エントリーDOI: 10.2210/pdb5i23/pdb
• 分子名称: Oligosaccharide 4-alpha-D-glucosyltransferase, TETRAETHYLENE GLYCOL, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: alpha glycosidase, cyclophellitol aziridine, inhibitor, probe, transferase
• 由来する生物種: Cellvibrio japonicus (strain Ueda107)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 95834.87

構造登録者

Wu, L.,Davies, G.J. (登録日: 2016-02-08, 公開日: 2016-05-04, 最終更新日: 2024-01-10)

主引用文献

Jiang, J.,Kuo, C.L.,Wu, L.,Franke, C.,Kallemeijn, W.W.,Florea, B.I.,van Meel, E.,van der Marel, G.A.,Codee, J.D.,Boot, R.G.,Davies, G.J.,Overkleeft, H.S.,Aerts, J.M.
Detection of Active Mammalian GH31 alpha-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.
Acs Cent.Sci., 2:351-358, 2016

PubMed Abstract: The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. α-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the lysosomal acid α-glucosidase (GAA) causes the lysosomal glycogen storage disorder, Pompe disease. Here, we design a synthetic route for fluorescent and biotin-modified ABPs for in vitro and in situ monitoring of α-glucosidases. We show, through mass spectrometry, gel electrophoresis, and X-ray crystallography, that α-glucopyranose configured cyclophellitol aziridines label distinct retaining α-glucosidases including GAA and ER α-glucosidase II, and that this labeling can be tuned by pH. We illustrate a direct diagnostic application in Pompe disease patient cells, and discuss how the probes may be further exploited for diverse applications.

PubMed: 27280170
DOI: 10.1021/acscentsci.6b00057

実験手法

X-RAY DIFFRACTION (1.95 Å)