Mechanisms, biology and inhibitors of deubiquitinating enzymes

Nat Chem Biol. 2007 Nov;3(11):697-705. doi: 10.1038/nchembio.2007.43.


The addition of ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers to proteins serves to modulate function and is a key step in protein degradation, epigenetic modification and intracellular localization. Deubiquitinating enzymes and Ubl-specific proteases, the proteins responsible for the removal of Ub and Ubls, act as an additional level of control over the ubiquitin-proteasome system. Their conservation and widespread occurrence in eukaryotes, prokaryotes and viruses shows that these proteases constitute an essential class of enzymes. Here, we discuss how chemical tools, including activity-based probes and suicide inhibitors, have enabled (i) discovery of deubiquitinating enzymes, (ii) their functional profiling, crystallographic characterization and mechanistic classification and (iii) development of molecules for therapeutic purposes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biology*
  • Endopeptidases / chemistry
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Kinetics
  • Phylogeny
  • Ubiquitin-Specific Proteases


  • Enzyme Inhibitors
  • Endopeptidases
  • Ubiquitin-Specific Proteases