Covalent Probes for Carbohydrate-Active Enzymes: From Glycosidases to Glycosyltransferases

Methods Enzymol. 2018:598:237-265. doi: 10.1016/bs.mie.2017.06.016. Epub 2017 Oct 31.

Abstract

Covalent probes for glycosidases and glycosyltransferases are of great interest as tool compounds for chemical biology. For glycosidases, a sizable number of such probes have been developed from covalent glycosidase inhibitors. We review selected recent examples and highlight different design strategies, including probes based on photoaffinity labels and mechanism-based inhibitors, as well as their applications in biology and for activity-based protein profiling. In contrast to glycosidases, only a limited number of covalent probes have been reported to date for glycosyltransferases. We describe a new class of covalent probes for the retaining α-1,4-galactosyltransferase LgtC from Neisseria meningitidis. On the basis of these probes, we have developed an operationally simple two-step protocol for the fluorescent labeling of recombinant LgtC both in purified form and in cell lysates. In principle, our approach is also applicable to other bacterial glycosyltransferases. Among other applications, our protocol may therefore be particularly useful for imaging of the differential expression of these enzymes in different bacterial species and strains.

Keywords: Covalent probe; Glycosidase; Glycosyltransferase; Inhibitor; Labeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins / chemistry*
  • Carbohydrates / chemistry
  • Fluorescent Dyes / chemistry
  • Glycoside Hydrolases / chemistry*
  • Glycosyltransferases / chemistry*
  • Models, Molecular
  • Molecular Probes / chemistry*
  • Neisseria meningitidis / chemistry*
  • Photoaffinity Labels / chemistry
  • Recombinant Proteins / chemistry
  • Staining and Labeling / instrumentation
  • Staining and Labeling / methods

Substances

  • Bacterial Proteins
  • Carbohydrates
  • Fluorescent Dyes
  • Molecular Probes
  • Photoaffinity Labels
  • Recombinant Proteins
  • Glycosyltransferases
  • LgtC protein, Neisseria
  • Glycoside Hydrolases