Structural and Kinetic Analysis of Free Methionine-R-sulfoxide Reductase from Staphylococcus aureus

Bong, Seoung Min; Kwak, Geun Hee; Moon, Jin Ho; Lee, Ki Seog; Kim, Hong Seok; Kim, Hwa Young; Min, Young

doi:10.1074/jbc.m110.103119

Cited by 14 publications

(4 citation statements)

References 37 publications

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“…aureus strain COL) that codes for a protein that reduces the free methionine sulfoxide. Although the structural and biochemical properties of this protein have been determined [ 40 ], its physiological relevance is unclear. The extent of expression of S .…”

Section: Discussionmentioning

confidence: 99%

Significance of Four Methionine Sulfoxide Reductases in Staphylococcus aureus

et al. 2015

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Staphylococcus aureus is a major human pathogen and emergence of antibiotic resistance in clinical staphylococcal isolates raises concerns about our ability to control these infections. Cell wall-active antibiotics cause elevated synthesis of methionine sulfoxide reductases (Msrs: MsrA1 and MsrB) in S. aureus. MsrA and MsrB enzymes reduce S-epimers and R-epimers of methionine sulfoxide, respectively, that are generated under oxidative stress. In the S. aureus chromosome, there are three msrA genes (msrA1, msrA2 and msrA3) and one msrB gene. To understand the precise physiological roles of Msr proteins in S. aureus, mutations in msrA1, msrA2 and msrA3 and msrB genes were created by site-directed mutagenesis. These mutants were combined to create a triple msrA (msrA1, msrA2 and msrA3) and a quadruple msrAB (msrA1, msrA2, msrA3, msrB) mutant. These mutants were used to determine the roles of Msr proteins in staphylococcal growth, antibiotic resistance, adherence to human lung epithelial cells, pigment production, and survival in mice relative to the wild-type strains. MsrA1-deficient strains were sensitive to oxidative stress conditions, less pigmented and less adherent to human lung epithelial cells, and showed reduced survival in mouse tissues. In contrast, MsrB-deficient strains were resistant to oxidants and were highly pigmented. Lack of MsrA2 and MsrA3 caused no apparent growth defect in S. aureus. In complementation experiments with the triple and quadruple mutants, it was MsrA1 and not MsrB that was determined to be critical for adherence and phagocytic resistance of S. aureus. Overall, the data suggests that MsrA1 may be an important virulence factor and MsrB probably plays a balancing act to counter the effect of MsrA1 in S. aureus.

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Section: Discussionmentioning

confidence: 99%

Significance of Four Methionine Sulfoxide Reductases in Staphylococcus aureus

et al. 2015

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“…TafRMSR is instead proposed to use a separate thiol to resolve the Cys A active site. By contrast, bacterial and yeast fRMSR enzymes form intrachain disulfide bonds between catalytic and resolving cysteine residues (Cys A -Cys R ) in the catalytic mechanism of MetO reduction [ 10 , 45 , 46 , 47 ].…”

Section: Archaeal Msr Enzymes Characterizedmentioning

confidence: 99%

Methionine Sulfoxide Reductases of Archaea

Maupin-Furlow

2018

Antioxidants

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Methionine sulfoxide reductases are found in all domains of life and are important in reversing the oxidative damage of the free and protein forms of methionine, a sulfur containing amino acid particularly sensitive to reactive oxygen species (ROS). Archaea are microbes of a domain of life distinct from bacteria and eukaryotes. Archaea are well known for their ability to withstand harsh environmental conditions that range from habitats of high ROS, such as hypersaline lakes of intense ultraviolet (UV) radiation and desiccation, to hydrothermal vents of low concentrations of dissolved oxygen at high temperature. Recent evidence reveals the methionine sulfoxide reductases of archaea function not only in the reduction of methionine sulfoxide but also in the ubiquitin-like modification of protein targets during oxidative stress, an association that appears evolutionarily conserved in eukaryotes. Here is reviewed methionine sulfoxide reductases and their distribution and function in archaea.

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“…A free methionine- R -sulfoxide reductase (MsrC) was first characterized by Lin and colleagues in E. coli [10] , and was subsequently purified from N. meningitidis and from S. aureus . High substrate specificity for free Met- R -SO was reported in all three bacterial organisms, and detailed analysis with respect to biochemical properties and structural composition was carried out [10] , [21] , [22] . Lee and Gladyshev described MsrC as a highly specific Msr for free Met- R -SO that does not reduce peptidyl methionine sulfoxides, and compensates for the low or missing activity of MsrB with respect to free Met- R -SO [34] .…”

Section: Discussionmentioning

confidence: 99%

“…There are even less data available on the role of MsrC in bacterial pathogenesis. Recently its ability to be stereo and size specific exclusively for the reduction of free Met- R -SO has been described in S. aureus , E. coli , N. meningitides and in Saccharomyces ( S. ) cerevisiae [10] , [11] , [21] , [22] . However, except for S. cerevisiae a role of MsrC in oxidative response has not been reported in these organisms.…”

Section: Introductionmentioning

confidence: 99%

Methionine Sulfoxide Reductases Are Essential for Virulence of Salmonella Typhimurium

et al. 2011

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Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H2O2, and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H2O2, as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium.

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Structural and Kinetic Analysis of Free Methionine-R-sulfoxide Reductase from Staphylococcus aureus

Cited by 14 publications

References 37 publications

Significance of Four Methionine Sulfoxide Reductases in Staphylococcus aureus

Significance of Four Methionine Sulfoxide Reductases in Staphylococcus aureus

Methionine Sulfoxide Reductases of Archaea

Methionine Sulfoxide Reductases Are Essential for Virulence of Salmonella Typhimurium

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