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

David H. Kwan, Yi Jin, Jianbing Jiang, Hong-Ming Chen, Miriam P. Kötzler, Herman S. Overkleeft, Gideon J. Davies, Stephen G. Withers

Research output: Contribution to journalLetterpeer-review

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-?-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.
Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalFEBS Letters
Volume590
Issue number4
DOIs
Publication statusPublished - 2016

Keywords

  • activity-based probes
  • CAZy GH1
  • epoxides
  • Glycosidase inhibitors
  • sugar-6-phosphate

Fingerprint

Dive into the research topics of 'Chemoenzymatic synthesis of 6-phospho-cyclophellitol as a novel probe of 6-phospho-β-glucosidases'. Together they form a unique fingerprint.

Cite this