title: Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A.
abstract: Methionine sulfoxide reductase A has long been known to reduce S-methionine sulfoxide, both as a free amino acid and within proteins. Recently the enzyme was shown to be bidirectional, capable of oxidizing free methionine and methionine in proteins to S-methionine sulfoxide. A feasible mechanism for controlling the directionality has been proposed, raising the possibility that reversible oxidation and reduction of methionine residues within proteins is a redox-based mechanism for cellular regulation. We undertook studies aimed at identifying proteins that are subject to site-specific, stereospecific oxidation and reduction of methionine residues. We found that calmodulin, which has nine methionine residues, is such a substrate for methionine sulfoxide reductase A. When calmodulin is in its calcium-bound form, Met77 is oxidized to S-methionine sulfoxide by methionine sulfoxide reductase A. When methionine sulfoxide reductase A operates in the reducing direction, the oxidized calmodulin is fully reduced back to its native form. We conclude that reversible covalent modification of Met77 may regulate the interaction of calmodulin with one or more of its many targets.
authors.affiliation: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jung Chae
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Geumsoo
authors.initials: G
authors.lastname: Kim
authors.affiliation: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rlevine@nih.gov.
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry*; D002846:Chromatography, Affinity; D047468:Immunoprecipitation; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D002147:Calmodulin; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D002118:Calcium
keywords: Calmodulin; Free radicals; Methionine oxidation; Methionine reduction; Methionine sulfoxide reductase; Signaling