Modulating protein activity and cellular function by methionine residue oxidation

Amino Acids. 2012 Aug;43(2):505-17. doi: 10.1007/s00726-011-1175-9. Epub 2011 Dec 7.


The sulfur-containing amino acid residue methionine (Met) in a peptide/protein is readily oxidized to methionine sulfoxide [Met(O)] by reactive oxygen species both in vitro and in vivo. Methionine residue oxidation by oxidants is found in an accumulating number of important proteins. Met sulfoxidation activates calcium/calmodulin-dependent protein kinase II and the large conductance calcium-activated potassium channels, delays inactivation of the Shaker potassium channel ShC/B and L-type voltage-dependent calcium channels. Sulfoxidation at critical Met residues inhibits fibrillation of atherosclerosis-related apolipoproteins and multiple neurodegenerative disease-related proteins, such as amyloid beta, α-synuclein, prion, and others. Methionine residue oxidation is also correlated with marked changes in cellular activities. Controlled key methionine residue oxidation may be used as an oxi-genetics tool to dissect specific protein function in situ.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apolipoproteins / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / chemistry
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Humans
  • Methionine / analogs & derivatives
  • Methionine / metabolism*
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Potassium Channels / metabolism
  • Prions / metabolism
  • Protein Multimerization
  • Reactive Oxygen Species / metabolism
  • alpha-Synuclein / metabolism


  • Amyloid beta-Peptides
  • Apolipoproteins
  • Potassium Channels
  • Prions
  • Reactive Oxygen Species
  • alpha-Synuclein
  • Methionine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • methionine sulfoxide