Substrates of the methionine sulfoxide reductase system and their physiological relevance.
Posttranslational modifications can change a protein's structure, function, and solubility. One specific modification caused by reactive oxygen species is the oxidation of the sulfur atom in the methionine (Met) side chain. This modified amino acid is denoted as methionine sulfoxide (MetO). MetOs in proteins are of considerable interest as they are involved in early posttranslational modification events. Thus, various organisms produce specific enzymes that can reverse these modifications. MetO reductases, known collectively as the methionine sulfoxide reductase (Msr) system, are the only known enzymes that can reduce MetOs. The current research field of Met redox cycles is consumed with elucidating its role in regulation, redox homeostasis, prevention of irreversible modifications, pathogenesis, and the aging process. Substrates of the Msr system can be loosely classified by the overall effect of the MetO on the protein. Regulated substrates utilize Met as a molecular switch to modulate activation; scavenging substrates use Mets to detoxify oxidants and protect important regions of the protein; and modified substrates are altered by Met oxidation resulting in various changes in their properties, including function, activity, structure, and degradation resistance.
Oien
Derek B
DB
Department of Pharmacology & Toxicology, School of Pharmacy University of Kansas, Lawrence, Kansas 66045, USA.
Moskovitz
Jackob
J
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D013379:Substrate Specificity
D004798:Enzymes; D016166:Free Radical Scavengers; D006728:Hormones; D015843:Serpins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C013111:methionine sulfoxide