A Specific Activity‐Based Probe to Monitor Family GH59 Galactosylceramidase, the Enzyme Deficient in Krabbe Disease

Marques, André R. A.; Willems, Lianne I.; Moro, Daniela Herrera; Florea, Bogdan I.; Scheij, Saskia; Ottenhoff, Roelof; Roomen, Cindy P. A. A. van; Verhoek, Marri; Nelson, Jessica K.; Kallemeijn, Wouter W.; Biela-Banaś, Anna; Martin, Olivier R.; Cachón‐González, M. Begoña; Kim, Nee Na; Cox, Timothy M.; Boot, Rolf G.; Overkleeft, Herman S.; Aerts, Johannes M. F. G.

doi:10.1002/cbic.201600561

Cited by 21 publications

(15 citation statements)

References 47 publications

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“…ABPP using cyclophellitol-derived probes allows for rapid evaluation GBA activity in patient tissues, and can identify GBA G samples with sensitivity comparable to immunoblotting (a considerably more laborious technique) [10]. Use of suitably configured ABPs has also demonstrated that lysosomal -glucosidase, lysosomal -galactocerebrosidase, and lysosomal -galactosidase are all amenable to ABPP profiling, opening up avenues for the rapid diagnosis of Pompe [34], Krabbe [50] and Fabry [32] diseases respectively. Interestingly, the irreversible inhibitory nature of many ABPs can also be used to in vivo.…”

Section: Recent Developments In the Glycosidase Abp Field 41 Glycosmentioning

confidence: 99%

An overview of activity-based probes for glycosidases

Armstrong

Schröder

et al. 2019

Current Opinion in Chemical Biology

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As the scope of modern genomics technologies increases, so does the need for informative chemical tools to study functional biology. Activity-based probes (ABPs) provide a powerful suite of reagents to probe the biochemistry of living organisms. These probes, featuring a specificity motif, a reactive chemical group and a reporter tag, are opening-up large swathes of protein chemistry to investigation in vitro, as well as in cellular extracts, cells and living organisms in vivo. Glycoside hydrolases, by virtue of their prominent biological and applied roles, provide a broad canvas on which ABPs may illustrate their functions. Here we provide an overview of glycosidase ABP mechanisms, and review recent ABP work in the glycoside hydrolase field, encompassing their use in medical diagnosis, their application for generating chemical genetic disease models, their fine-tuning through conformational and reactivity insight, their use for high-throughput inhibitor discovery, and their deployment for enzyme discovery and dynamic characterization. Highlights  Glycosidases carry out many essential functions across all domains of life  Activity-based probes can interrogate complex biological samples for glycosidase activity  Glycosidase probes can characterize enzymes of biomedical/biotechnological interest  Analysis of conformational itineraries may inform the design of future probes.  Activity-based probes assist high-throughput discovery of inhibitors

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Section: Recent Developments In the Glycosidase Abp Field 41 Glycosmentioning

confidence: 99%

An overview of activity-based probes for glycosidases

Armstrong

Schröder

et al. 2019

Current Opinion in Chemical Biology

View full text Add to dashboard Cite

show abstract

“…Subsequently, cyclophellitol aziridine ABPs with attached reporter groups via alkyl or acyl linkers were designed reacting with multiple retaining glycosidases in the same class [55,59]. Cyclophellitol aziridine ABPs labeling α-galactosidases, α-glucosidases, α-fucosidase, α-iduronidase, β-galactosidases, and β-glucuronidase, as well as cyclophellitol ABPs labelling galactocerebrosidase, were designed [60][61][62][63][64][65]. Applications of ABPs are the quantitative detection and localization of glycosidases in cells and tissues, as well as identification and characterization of glycosidase inhibitors by competitive ABP profiling [66,67].…”

Section: Gcase Protein and Life Cyclementioning

confidence: 99%

Glucocerebrosidase: Functions in and Beyond the Lysosome

Boer

Smeden

Bouwstra

et al. 2020

JCM

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Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.

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“…A variety of ABPs have been described for different enzyme classes (Table 1) 8,9 . An ABP can be specific for one enzyme (tailored probe) 10 or can target a group of enzymes sharing recognition or reactivity (broad-spectrum probe) 11 . Broad-spectrum probes can be used for competitive ABPP (Fig.…”

Section: Abppmentioning

confidence: 99%

Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification

et al. 2018

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Activity-based protein profiling (ABPP) has emerged as a valuable chemical proteomics method to guide the therapeutic development of covalent drugs by assessing their on-target engagement and off-target activity. We recently used ABPP to determine the serine hydrolase interaction landscape of the experimental drug BIA 10-2474, thereby providing a potential explanation for the adverse side effects observed with this compound. ABPP allows mapping of protein interaction landscapes of inhibitors in cells, tissues and animal models. Whereas our previous protocol described quantification of proteasome activity using stable-isotope labeling, this protocol describes the procedures for identifying the in vivo selectivity profile of covalent inhibitors with label-free quantitative proteomics. The optimization of our protocol for label-free quantification methods results in high proteome coverage and allows the comparison of multiple biological samples. We demonstrate our protocol by assessing the protein interaction landscape of the diacylglycerol lipase inhibitor DH376 in mouse brain, liver, kidney and testes. The stages of the protocol include tissue lysis, probe incubation, target enrichment, sample preparation, liquid chromatography-mass spectrometry (LC-MS) measurement, data processing and analysis. This approach can be used to study target engagement in a native proteome and to identify potential off targets for the inhibitor under investigation. The entire protocol takes at least 4 d, depending on the number of samples.

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A Specific Activity‐Based Probe to Monitor Family GH59 Galactosylceramidase, the Enzyme Deficient in Krabbe Disease

Cited by 21 publications

References 47 publications

An overview of activity-based probes for glycosidases

An overview of activity-based probes for glycosidases

Glucocerebrosidase: Functions in and Beyond the Lysosome

Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification

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