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© Research
Event

Joint seminar department of Cell Biology and infection and Department of Structural Biology and Chemistry: Herman Overkleeft, Activity-based glycosidase profiling in biomedicine and biotechnology

Scientific Fields
Diseases
Organisms
Applications
Technique
Date
22
Oct 2019
Time
14:00:00
28 Rue du Dr Roux, Paris, France
Address
Building: François Jacob Room: François Jacob auditorium
Location
2019-10-22 14:00:00 2019-10-22 15:30:00 Europe/Paris Joint seminar department of Cell Biology and infection and Department of Structural Biology and Chemistry: Herman Overkleeft, Activity-based glycosidase profiling in biomedicine and biotechnology Department of Cell Biology and Infection Department of Structural Biology and Chemistry JOINT  SEMINAR Tuesday 22 october 2019 at 2.00 pm AUDITORIUM CENTRE F. JACOB room- CFJ RdC 17 Herman Overkleeft Leiden Institute of […] 28 Rue du Dr Roux, Paris, France Paola Arimondo paola.arimondo@pasteur.fr

About

Department of Cell Biology and Infection
Department of Structural Biology and Chemistry
JOINT  SEMINAR

Tuesday 22 october 2019 at 2.00 pm
AUDITORIUM CENTRE F. JACOB room- CFJ RdC 17
Herman Overkleeft
Leiden Institute of Chemistry, Leiden University
h.s.overkleeft@chem.leidenuniv.nl

 

Activity-based glycosidase profiling in biomedicine and biotechnology

 Activity-based protein profiling (ABPP) is a rapidly emerging field in chemical biology research. Enzymes that employ a mechanism in processing their substrate that involves formation of a covalent enzyme-intermediate adduct can be blocked by mechanism-based suicide inhibitors: compounds that react within the enzyme active site to form a covalent and irreversible adduct. Introduction of a reporter moiety (‘TAG’ in the below picture) yields an activity-based probe (ABP) through which enzyme activities can be discovered (comparative ABPP) and the efficacy enzyme inhibitors in complex biological systems analyzed (competitive ABPP).

Our work on ABPP development focuses on retaining glycosidases: hydrolytic enzymes able to cleave interglycosidic linkages and that do so through the formation of covalent enzymesubstrate intermediates. Configurational and functional analogues of the natural product and mechanism-based retaining beta-glucosidase inhibitor, cyclophellitol, prove to be highly versatile tools to study retaining glycosidases of various nature and origin in relation to human health and disease, but also in the field of biotechnology. In this lecture the current state in the design, synthesis and application of synthetic cyclophellitol derivatives in studying retaining glycosidases will be presented. Discussed subjects will include 1) diagnosis of human lysosomal exoglycosidases in relation to lysosomal storage disorders; 2) glycosylation of cyclophellitol derivatives top arrive at retaining endoglycosidase ABPs and 3) application of glycosidase ABPs in the functional profiling of fungal secretomes for the discovery of glycosidases for biotechnology application.

References

1) M. D. Witte, W. W. Kallemeijn, J. Aten, K.-Y. Li, A. Strijland, W. E. Donker-Koopman, B. Blijlevens, G. Kramer, A. M. C. H. van den Nieuwendijk, B. I. Florea, B. Hooibrink, C. E. M. Hollak, R. Ottenhoff, R. G. Boot, G.
van der Marel, H. S. Overkleeft and J. M. F. G. Aerts, Ultrasensitive in situ visualization of active glucocerebrosidase molecules, Nat. Chem. Biol. 2010, 6, 907-913.

2) J. Jiang, C.-L. Kuo, L. Wu, C. Franke, W. W. Kallemeijn, B. I. Florea, E. van Meel, G. A. van der Marel, J. D. C. Codée, R. G. Boot, G. J. Davies, H. S. Overkleeft and J. M. F. G. Aerts, Detection of active mammalian
GH31 alpha-glucosidases in health and disease using in-class, broad-spectrum activity-based probes, ACS Cent. Sci. 2016, 2, 351-358.

3) L. Wu, J. Jiang, Y. Jin, W. W. Kallemeijn, C.-L. Kuo, M. Artola, W. Dai, C. van Elk, M. van Eijk, G. A. van der Marel, J. D. C. Codée, B. I. Florea, J. M. F. G. Aerts, H. S. Overkleeft and G. J. Davies, Activity-based probes forfunctional interrogation of retaining beta-glucuronidases, Nat. Chem. Biol. 2017, 13, 867-873.

4) S. P. Schröder, C. de Boer, N. G. S. McGregor, R. J. Rowland, O. Moroz, E. Blagova, J. Reijngoud, M.  Arentshorst, D. Osborn, M. D. Morant, E. Abbate, M. A. Stringer, K. B. R. M. Krogh, L. Raich, C. Rovira, J.-G. Berrin, G. P. van Wezel, A. F. J. Ram, B. I. Florea, G. A. van der Marel, J. D. C. Codée, K. S. Wilson, L. Wu, G. J.  Davies and H. S. Overkleeft, Dynamic and functional profiling of xylan-degrading enzymes in Aspergillus secretomes using activity-based probes, ACS Cent. Sci 2019, 5, 1067-1078.

Contacts :

Guillaume Dumenil
Unité de Pathogénèse des infections vasculaires
Guillaume.dumenil@pasteur.fr

Paola Arimondo
Unité Chimie Biologique Epigénétique
Paola.arimondo@pasteur.fr

Location

Building: François Jacob
Room: François Jacob auditorium
Address: 28 Rue du Dr Roux, Paris, France