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In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 a-Lfucosidases
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.
Diamond Keywords: Enzymes
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I03-Macromolecular Crystallography
Added On:
29/09/2015 10:08
Documents:
c4sc03739a.pdf
Discipline Tags:
Biochemistry
Chemistry
Structural biology
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)