title: Kinetic characterization of the catalytic mechanism of methionine sulfoxide reductase B from Neisseria meningitidis.
abstract: Methionine sulfoxide reductases catalyze the thioredoxin-dependent reduction of methionine sulfoxide back to methionine. The methionine sulfoxide reductases family is composed of two structurally unrelated classes of enzymes named MsrA and MsrB, which display opposite stereoselectivities toward the sulfoxide function. Both enzymes are monomeric and share a similar three-step chemical mechanism. First, in the reductase step, a sulfenic acid intermediate is formed with a concomitant release of 1 mol of methionine per mol of enzyme. Then, an intradisulfide bond is formed. Finally, Msrs return back to reduced forms via reduction by thioredoxin. In the present study, it is shown for the Neisseria meningitidis MsrB that (1) the reductase step is rate-determining in the process leading to formation of the disulfide bond and (2) the thioredoxin-recycling process is rate-limiting. Moreover, the data suggest that within the thioredoxin-recycling process, the rate-limiting step takes place after the two-electron chemical exchange and thus is associated with the release of oxidized thioredoxin.
authors.affiliation: UMR 7567 CNRS-UHP, Maturation of ARN and Molecular Enzymology, Faculty of Sciences, Boulevard des Aiguillettes, BP 239, 54506 Vandoeuvre-lès-Nancy, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Olry
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boschi-Muller
authors.forename: Guy
authors.initials: G
authors.lastname: Branlant
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D003545:Cysteine / Q000235:genetics; D004220:Disulfides / Q000378:metabolism; D007700:Kinetics; D008715:Methionine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D016297:Mutagenesis, Site-Directed; D009345:Neisseria meningitidis / Q000201:enzymology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics; D013434:Sulfenic Acids / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004220:Disulfides; D013434:Sulfenic Acids; D012694:Serine; D013879:Thioredoxins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D003545:Cysteine; C013111:methionine sulfoxide