scholarly journals A Sulfenic Acid Enzyme Intermediate Is Involved in the Catalytic Mechanism of Peptide Methionine Sulfoxide Reductase fromEscherichia coli

2000 ◽  
Vol 275 (46) ◽  
pp. 35908-35913 ◽  
Author(s):  
Sandrine Boschi-Muller ◽  
Said Azza ◽  
Sarah Sanglier-Cianferani ◽  
François Talfournier ◽  
Alain Van Dorsselear ◽  
...  
Keyword(s):  
Catalytic Mechanism ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Sulfenic Acid ◽  
Fromescherichia Coli ◽  
Enzyme Intermediate ◽  
Peptide Methionine Sulfoxide Reductase

scholarly journals Molecular Mechanisms of the Methionine Sulfoxide Reductase System from Neisseria meningitidis

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 131 ◽  
Author(s):  
Sandrine Boschi-Muller
Keyword(s):  
Oxidative Stress ◽  
Neisseria Meningitidis ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Catalytic Mechanism ◽  
Methionine Sulfoxide ◽  
Pathogenic Bacterium ◽  
Methionine Sulfoxide Reductase ◽  
Sulfenic Acid ◽  
Methionine Residues

Neisseria meningitidis, an obligate pathogenic bacterium in humans, has acquired different defense mechanisms to detect and fight the oxidative stress generated by the host’s defense during infection. A notable example of such a mechanism is the PilB reducing system, which repairs oxidatively-damaged methionine residues. This review will focus on the catalytic mechanism of the two methionine sulfoxide reductase (MSR) domains of PilB, which represent model enzymes for catalysis of the reduction of a sulfoxide function by thiols through sulfenic acid chemistry. The mechanism of recycling of these MSR domains by various “Trx-like” disulfide oxidoreductases will also be discussed.

scholarly journals Staphylococcus aureus peptide methionine sulfoxide reductases protect from human whole blood killing.

2021 ◽  
Author(s):  
William N. Beavers ◽  
Ashley L. DuMont ◽  
Andrew J. Monteith ◽  
K. Nichole Maloney ◽  
Keri A. Tallman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Protein Oxidation ◽  
Whole Blood ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Human Whole Blood ◽  
Infection Models ◽  
Intraperitoneal Infection ◽  
Peptide Methionine Sulfoxide Reductase

The generation of oxidative stress is a host strategy used to control Staphylococcus aureus infections. Sulfur containing amino acids, cysteine and methionine, are particularly susceptible to oxidation because of the inherent reactivity of sulfur. Due to the constant threat of protein oxidation, many systems evolved to protect S. aureus from protein oxidation or to repair protein oxidation after it occurs. The S. aureus peptide methionine sulfoxide reductase (Msr) system reduces methionine sulfoxide to methionine. Staphylococci have four Msr enzymes, which all perform this reaction. Deleting all four msr genes in USA300 LAC (Δmsr) sensitizes S. aureus to hypochlorous acid (HOCl) killing, however, Δmsr does not exhibit increased sensitivity to H2O2 stress or superoxide anion stress generated by paraquat or pyocyanin. Consistent with increased susceptibility to HOCl killing, Δmsr is slower to recover following co-culture with both murine and human neutrophils than USA300 wildtype. Δmsr is attenuated for dissemination to the spleen following murine intraperitoneal infection and exhibits reduced bacterial burdens in a murine skin infection model. Notably, no differences in bacterial burdens were observed in any organ following murine intravenous infection. Consistent with these observations, USA300 wildtype and Δmsr have similar survival phenotypes when incubated with murine whole blood. However, Δmsr is killed more efficiently by human whole blood. These findings indicate that species-specific immune cell composition of the blood may influence the importance of Msr enzymes during S. aureus infection of the human host. IMPORTANCE Oxidative stress is a host defense strategy to control bacterial infections, and bacteria have evolved systems to counteract this innate immune defense. Here we investigate the peptide methionine sulfoxide reductase system in Staphylococcus aureus that repairs oxidized methionine residues in proteins, preventing the need to resynthesize damaged proteins de novo. Most organisms have an Msr system, and in S. aureus these enzymes are protective against HOCl killing, the major oxidant produced by neutrophils. The S. aureus Msr system does not have a significant contribution to pathogenesis in bacteremia murine infection models but does protect S. aureus in both skin and intraperitoneal infection models. Strains lacking Msr activity are killed equivalently to wildtype by murine whole blood, and Δmsr is more sensitive to killing by human whole blood than the wildtype strain. These data identify the Msr enzymes as important and potentially specific factors for S. aureus pathogenesis in the human host.

scholarly journals Methionine sulfoxide reductase B from Corynebacterium diphtheriae catalyzes sulfoxide reduction via an intramolecular disulfide cascade

2020 ◽  
Vol 295 (11) ◽  
pp. 3664-3677
Author(s):  
Maria-Armineh Tossounian ◽  
Anh-Co Khanh Truong ◽  
Lieven Buts ◽  
Khadija Wahni ◽  
Álvaro Mourenza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quantum Coherence ◽  
Solution Structure ◽  
Structural Changes ◽  
Catalytic Mechanism ◽  
Methionine Sulfoxide ◽  
Structural Rearrangement ◽  
Corynebacterium Diphtheriae ◽  
Methionine Sulfoxide Reductase ◽  
Bacterial Survival

Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune system-induced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation. Here, we solved the solution structure of C. diphtheriae MsrB (Cd-MsrB) and unraveled its catalytic and oxidation-protection mechanisms. Cd-MsrB catalyzes methionine sulfoxide reduction involving three redox-active cysteines. Using NMR heteronuclear single-quantum coherence spectra, kinetics, biochemical assays, and MS analyses, we show that the conserved nucleophilic residue Cys-122 is S-sulfenylated after substrate reduction, which is then resolved by a conserved cysteine, Cys-66, or by the nonconserved residue Cys-127. We noted that the overall structural changes during the disulfide cascade expose the Cys-122–Cys-66 disulfide to recycling through thioredoxin. In the presence of hydrogen peroxide, Cd-MsrB formed reversible intra- and intermolecular disulfides without losing its Cys-coordinated Zn2+, and only the nonconserved Cys-127 reacted with the low-molecular-weight (LMW) thiol mycothiol, protecting it from overoxidation. In summary, our structure-function analyses reveal critical details of the Cd-MsrB catalytic mechanism, including a major structural rearrangement that primes the Cys-122–Cys-66 disulfide for thioredoxin reduction and a reversible protection against excessive oxidation of the catalytic cysteines in Cd-MsrB through intra- and intermolecular disulfide formation and S-mycothiolation.

A Structural Analysis of the Catalytic Mechanism of Methionine Sulfoxide Reductase A from Neisseria meningitidis

2008 ◽  
Vol 377 (1) ◽  
pp. 268-280 ◽  
Author(s):  
Fanomezana M. Ranaivoson ◽  
Mathias Antoine ◽  
Brice Kauffmann ◽  
Sandrine Boschi-Muller ◽  
André Aubry ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Neisseria Meningitidis ◽  
Catalytic Mechanism ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Sulfoxide Reductase A
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