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Chemoenzymatic synthesis of 6-phospho-cyclophellitol as a novel probe of 6-phospho-beta-glucosidases

TitleChemoenzymatic synthesis of 6-phospho-cyclophellitol as a novel probe of 6-phospho-beta-glucosidases
Publication TypeJournal Article
Year of Publication2016
AuthorsKwan, DH, Jin, Y, Jiang, J, Chen, H-M, Koetzler, MP, Overkleeft, HS, Davies, GJ, Withers, SG
JournalFEBS LETTERS
Volume590
Pagination461-468
Date PublishedFEB
ISSN0014-5793
Abstract

Covalent, mechanism-based inhibitors of glycosidases are valuable probe molecules for visualizing enzyme activities in complex systems. We, here, describe the chemoenzymatic synthesis of 6-phospho-cyclophellitol and evaluate its behaviour as a mechanism-based inactivator of the Streptococcus pyogenes 6-phospho-beta-glucosidase from CAZy family GH1. We further present the three-dimensional structure of the inactivated enzyme, which reveals the constellation of active site residues responsible for the enzyme's specificity and confirms the covalent nature of the inactivation.

DOI10.1002/1873-3468.12059