1. Crystal Structure of the Escherichia coli Peptide Methionine Sulphoxide Reductase at 1.9 Å Resolution
- Author
-
Frédérique Tête-Favier, Sandrine Boschi-Muller, Guy Branlant, Saïd Azza, André Aubry, David Cobessi, Laboratoire de Cristallographie et modélisation des matériaux minéraux et biologiques (LCM3B), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), and Cristallographie et modélisation des matériaux minéraux et biologiques (CMMMB)
- Subjects
Models, Molecular ,Protein Folding ,Protein Conformation ,MESH: Sequence Homology, Amino Acid ,Sequence Homology ,MESH: Selenomethionine ,MESH: Amino Acid Sequence ,Reductase ,Crystallography, X-Ray ,chemistry.chemical_compound ,MESH: Protein Structure, Tertiary ,Protein structure ,MESH: Protein Conformation ,MESH: Structure-Activity Relationship ,Structural Biology ,Models ,Selenomethionine ,Peptide sequence ,MESH: Bacterial Proteins ,MESH: Evolution, Molecular ,chemistry.chemical_classification ,0303 health sciences ,Crystallography ,biology ,MAD ,MESH: Escherichia coli ,030302 biochemistry & molecular biology ,MsrA ,Amino acid ,Amino Acid ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,Biochemistry ,Oxidoreductases ,MESH: Models, Molecular ,MSRA ,α/β roll ,Protein Structure ,Stereochemistry ,Evolution ,Recombinant Fusion Proteins ,MESH: Protein Folding ,Molecular Sequence Data ,MESH: Sequence Alignment ,Catalysis ,peptide methionine sulphoxide reductase ,Evolution, Molecular ,03 medical and health sciences ,Structure-Activity Relationship ,Bacterial Proteins ,Species Specificity ,Escherichia coli ,MESH: Recombinant Fusion Proteins ,MESH: Species Specificity ,Amino Acid Sequence ,Cysteine ,MESH: Oxidoreductases ,catalytic cysteine residue ,Molecular Biology ,030304 developmental biology ,Methionine ,Binding Sites ,MESH: Molecular Sequence Data ,Sequence Homology, Amino Acid ,Active site ,Molecular ,MESH: Cysteine ,MESH: Catalysis ,MESH: Crystallography, X-Ray ,Protein Structure, Tertiary ,chemistry ,MESH: Binding Sites ,Methionine Sulfoxide Reductases ,biology.protein ,X-Ray ,Sequence Alignment ,Tertiary - Abstract
Background: Peptide methionine sulphoxide reductases catalyze the reduction of oxidized methionine residues in proteins. They are implicated in the defense of organisms against oxidative stress and in the regulation of processes involving peptide methionine oxidation/reduction. These enzymes are found in numerous organisms, from bacteria to mammals and plants. Their primary structure shows no significant similarity to any other known protein. Results: The X-ray structure of the peptide methionine sulphoxide reductase from Escherichia coli was determined at 3 A resolution by the multiple wavelength anomalous dispersion method for the selenomethionine-substituted enzyme, and it was refined to 1.9 A resolution for the native enzyme. The 23 kDa protein is folded into an α/β roll and contains a large proportion of coils. Among the three cysteine residues involved in the catalytic mechanism, Cys-51 is positioned at the N terminus of an α helix, in a solvent-exposed area composed of highly conserved amino acids. The two others, Cys-198 and Cys-206, are located in the C-terminal coil. Conclusions: Sequence alignments show that the overall fold of the peptide methionine sulphoxide reductase from E. coli is likely to be conserved in many species. The characteristics observed in the Cys-51 environment are in agreement with the expected accessibility of the active site of an enzyme that reduces methionine sulphoxides in various proteins. Cys-51 could be activated by the influence of an α helix dipole. The involvement of the two other cysteine residues in the catalytic mechanism requires a movement of the C-terminal coil. Several conserved amino acids and water molecules are discussed as potential participants in the reaction.
- Full Text
- View/download PDF