Reversible Methionine Residue Oxidation in Signalling Proteins and Methionine Sulfoxide Reductases

Sulphur-containing amino acid methionine is prone to oxidation to methionine-R,S-sulfoxide by reactive oxidative species (ROS) of both intracellular and extracellular origins.Peptide methionine oxidation results in significant changes in protein activity, such as reduced binding affinity for calmodulin-binding by oxidized calmodulin, activation of calcium/calmodulin-dependent protein kinase II, slowed inactivation of potassium channel ShC/B.In most organisms, there exist one msrA gene and one to three msrB genes (msrB1-3), encoding two sequence and structurally-unrelated enzymes:MsrA and MsrB, to reduce methionine-S-sulfoxide and methionine-R-sulfoxide respectively.Both enzymes have rather similar catalytic mechanisms, their reactive center conformations being mirror images.These two reductases are widely distributed in different mammalian organs and subcellular structures.MsrA activity and structure have been investigated in the last thirty years, it playing an important anti-oxidizing role in aging and in neurodegenerative diseases, but is a major virulence factor for pathogenic bacteria.MsrB has also received much attention in the last decade and significant progresses have been made.Roles of these enzymes in regulating activities of signal protein molecules are being gradually recognized.