<i>In vitro</i> and <i>in vivo</i> comparative and competitive activity-based protein profiling of GH29 α-l-fucosidases.

ABSTRACT: GH29 α-l-fucosidases catalyze the hydrolysis of α-l-fucosidic linkages. Deficiency in human lysosomal α-l-fucosidase (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 α-l-fucosidases from bacteria, mice and man. Crystallographic analysis on bacterial α-l-fucosidase confirms that the ABPs act by covalent modification of the active site nucleophile. Competitive activity-based protein profiling identified l-fuconojirimycin as the single GH29 α-l-fucosidase inhibitor from eight configurational isomers.

SUBMITTER: Jiang J 

PROVIDER: S-EPMC5654414 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature