O-GlcNAc peptide epoxyketones are recognized by mammalian proteasomes

J Am Chem Soc. 2009 Sep 2;131(34):12064-5. doi: 10.1021/ja901231w.

Abstract

Cytosolic and nuclear proteins may be subject to both O-GlcNAcylation and proteasomal degradation. By means of activity-based profiling, we demonstrate that O-GlcNAc serine-containing peptide epoxyketones bind to the proteasome catalytic active sites and thus provide the first clear evidence that proteasomes recognize peptides post-translationally modified with a GlcNAc moiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • Cell Line
  • Humans
  • Ketones / metabolism*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors
  • Protein Binding
  • Staining and Labeling

Substances

  • Ketones
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex
  • Acetylglucosamine