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In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 a-Lfucosidases

DOI: 10.1039/C4SC03739A DOI Help

Authors: Jianbing Jiang (Leiden University) , Wouter W. Kallemeijn (Academic Medical Center) , Daniel W. Wright (University of York) , Adrianus M. C. H. Van Den Nieuwendijk (Leiden University) , Veronica Coco Rohde (Leiden University) , Elisa Colomina Folch (Leiden University) , Hans Van Den Elst (Leiden University) , Bogdan I. Florea (Leiden University) , Saskia Scheij (Academic Medical Center) , Wilma E. Donker-koopman (Academic Medical Center) , Marri Verhoek (Academic Medical Center) , Nan Li (Leiden University) , Martin Schürmann (DSM Innovative Synthesis) , Daniel Mink (DSM Innovative Synthesis) , Rolf G. Boot (Academic Medical Center) , Jeroen D. C. Codée (Leiden University) , Gijsbert A. Van Der Marel (Leiden University) , Gideon J. Davies (University of York) , Johannes M. F. G. Aerts (Leiden University) , Herman S. Overkleeft (Leiden University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemical Science , VOL 6 (5) , PAGES 2782 - 2789

State: Published (Approved)
Published: June 2015
Diamond Proposal Number(s): 7864 , 9948

Abstract: GH29 a-L-fucosidases catalyze the hydrolysis of a-L-fucosidic linkages. Deficiency in human lysosomal a-Lfucosidase (FUCA1) leads to the recessively inherited disorder, fucosidosis. Herein we describe the development of fucopyranose-configured cyclophellitol aziridines as activity-based probes (ABPs) for selective in vitro and in vivo labeling of GH29 a-L-fucosidases from bacteria, mice and man. Crystallographic analysis on bacterial a-L-fucosidase confirms that the ABPs act by covalent modification f the active site nucleophile. Competitive activity-based protein profiling identified L-fuconojirimycin as the single GH29 a-L-fucosidase inhibitor from eight configurational isomers.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography