Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein

Bertrand Friguet, Luke I. Szweda

Research output: Contribution to journalArticlepeer-review

240 Scopus citations


Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.

Original languageEnglish (US)
Pages (from-to)21-25
Number of pages5
JournalFEBS Letters
Issue number1
StatePublished - Mar 17 1997


  • 4-Hydroxy-2-nonenal
  • Free radicals
  • Glucose-6-phosphate dehydrogenase
  • Hydrophobicity
  • Lipid peroxidation
  • Multicatalytic proteinase (20S proteasome)

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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