title: Recharging oxidative protein repair: catalysis by methionine sulfoxide reductases towards their amino acid, protein, and model substrates.
abstract: The sulfur-containing amino acid methionine (Met) in its free and amino acid residue forms can be readily oxidized to the R and S diastereomers of methionine sulfoxide (MetO). Methionine sulfoxide reductases A (MSRA) and B (MSRB) reduce MetO back to Met in a stereospecific manner, acting on the S and R forms, respectively. A third MSR type, fRMSR, reduces the R form of free MetO. MSRA and MSRB are spread across the three domains of life, whereas fRMSR is restricted to bacteria and unicellular eukaryotes. These enzymes protect against abiotic and biotic stresses and regulate lifespan. MSRs are thiol oxidoreductases containing catalytic redox-active cysteine or selenocysteine residues, which become oxidized by the substrate, requiring regeneration for the next catalytic cycle. These enzymes can be classified according to the number of redox-active cysteines (selenocysteines) and the strategies to regenerate their active forms by thioredoxin and glutaredoxin systems. For each MSR type, we review catalytic parameters for the reduction of free MetO, low molecular weight MetO-containing compounds, and oxidized proteins. Analysis of these data reinforces the concept that MSRAs reduce various types of MetO-containing substrates with similar efficiency, whereas MSRBs are specialized for the reduction of MetO in proteins.
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tarrago
authors.forename: V N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001686:Biological Phenomena; D002384:Catalysis; D020134:Catalytic Domain; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D011506:Proteins; D051150:Methionine Sulfoxide Reductases