4WSK

Crystal structure of a bacterial fucosidase with phenyl((1R,2R,3R,4R,5R,6R)-2,3,4-trihydroxy-5-methyl-7-azabicyclo[4.1.0]heptan-7-yl)methanone

Summary for 4WSK

• Entry DOI: 10.2210/pdb4wsk/pdb
• Descriptor: Alpha-L-fucosidase, SULFATE ION, N-[(1S,2R,3R,4S,5R)-3,4,5-trihydroxy-2-methylcyclohexyl]benzamide, ... (5 entities in total)
• Functional Keywords: fucosidase complex covalent inhibitor, hydrolase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 4
• Total formula weight: 218165.34

Authors

Davies, G.J. (deposition date: 2014-10-28, release date: 2014-11-12, Last modification date: 2024-01-10)

Primary citation

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.
In vitroandin vivocomparative and competitive activity-based protein profiling of GH29 alpha-l-fucosidases.
Chem Sci, 6:2782-false, 2015

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 and 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.

PubMed: 29142681
DOI: 10.1039/c4sc03739a

Experimental method

X-RAY DIFFRACTION (1.92 Å)