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Chemoenzymatic synthesis of 6‐phospho‐cyclophellitol as a novel probe of 6‐phospho‐β‐glucosidases
Author(s) -
Kwan David H.,
Jin Yi,
Jiang Jianbing,
Chen HongMing,
Kötzler Miriam P.,
Overkleeft Herman S.,
Davies Gideon J.,
Withers Stephen G.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12059
Subject(s) - enzyme , covalent bond , chemistry , streptococcus pyogenes , biochemistry , mechanism (biology) , active site , stereochemistry , glucosidases , bacteria , biology , organic chemistry , genetics , epistemology , staphylococcus aureus , philosophy
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‐β‐glucosidase from CAZ y family GH 1. 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.