Issue 5, 2015

In vitro and in vivo 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.

Graphical abstract: In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-l-fucosidases

Supplementary files

Article information

Article type
Edge Article
Submitted
03 Dec 2014
Accepted
09 Feb 2015
First published
09 Feb 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2015,6, 2782-2789

Author version available

In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-L-fucosidases

J. Jiang, W. W. Kallemeijn, D. W. Wright, A. M. C. H. van den Nieuwendijk, V. C. Rohde, E. C. Folch, H. van den Elst, B. I. Florea, S. Scheij, W. E. Donker-Koopman, M. Verhoek, N. Li, M. Schürmann, D. Mink, R. G. Boot, J. D. C. Codée, G. A. van der Marel, G. J. Davies, J. M. F. G. Aerts and H. S. Overkleeft, Chem. Sci., 2015, 6, 2782 DOI: 10.1039/C4SC03739A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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