Download MendeleyIn vitroandin vivocomparative and competitive activity-based protein profiling of GH29 alpha-l-fucosidases.
Jiang, J., Kallemeijn, W.W., Wright, D.W., van den Nieuwendijk, A.M.C.H., Rohde, V.C., Folch, E.C., van den Elst, H., Florea, B.I., Scheij, S., Donker-Koopman, W.E., Verhoek, M., Li, N., Schurmann, M., Mink, D., Boot, R.G., Codee, J.D.C., van der Marel, G.A., Davies, G.J., Aerts, J.M.F.G., Overkleeft, H.S.(2015) Chem Sci 6: 2782-false
- PubMed: 29142681
- DOI: https://doi.org/10.1039/c4sc03739a
- Primary Citation of Related Structures:
4WSJ, 4WSK - PubMed 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.
Organizational Affiliation:
Leiden Institute of Chemistry , Leiden University , P. O. Box 9502 , 2300 RA Leiden , The Netherlands . Email: h.s.overkleeft@chem.leidenuniv.nl ; Email: j.m.aerts@amc.uva.nl.
