title: Methionine sulfoxide reductase B displays a high level of flexibility.
abstract: Methionine sulfoxide reductases (Msrs) are enzymes that catalyze the reduction of methionine sulfoxide back to methionine. In vivo, Msrs are essential in the protection of cells against oxidative damage to proteins and in the virulence of some bacteria. Two structurally unrelated classes of Msrs, named MsrA and MsrB, exist. MsrB are stereospecific to R epimer on the sulfur of sulfoxide. All MsrB share a common reductase step with the formation of a sulfenic acid intermediate. For the subclass of MsrB whose recycling process passes through the formation of an intradisulfide bond, the recycling reducer is thioredoxin. In the present study, X-ray structures of Neisseria meningitidis MsrB have been determined. The structures have a fold based on two beta-sheets, similar to the fold already described for other MsrB, with the recycling Cys63 located in a position favorable for disulfide bond formation with the catalytic Cys117. X-ray structures of Xanthomonas campestris MsrB have also been determined. In the C117S MsrB structure with a bound substrate, the recycling Cys31 is far from Ser117, with Trp65 being essential in the reductase step located in between. This positioning prevents the formation of the Cys31-Cys117 disulfide bond. In the oxidized structure, a drastic conformational reorganization of the two beta-sheets due to withdrawal of the Trp65 region from the active site, which remains compatible with an efficient thioredoxin-recycling process, is observed. The results highlight the remarkable structural malleability of the MsrB fold.
authors.affiliation: CRM2, Equipe Biocristallographie, UMR 7036 CNRS-UHP, Institut Jean Barriol, Nancy Université, Faculté des Sciences et Techniques, BP 70239, 54506 Vandoeuvre-les-Nancy, France.
authors.forename: Fanomezana M
authors.initials: FM
authors.lastname: Ranaivoson
authors.forename: Fabrice
authors.initials: F
authors.lastname: Neiers
authors.forename: Brice
authors.initials: B
authors.lastname: Kauffmann
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boschi-Muller
authors.forename: Guy
authors.initials: G
authors.lastname: Branlant
authors.forename: Frédérique
authors.initials: F
authors.lastname: Favier
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine; D051150:Methionine Sulfoxide Reductases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000201:enzymology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry*; D018583:Pliability; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D016959:Xanthomonas campestris / Q000201:enzymology*
chemical_list: D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D003545:Cysteine