scholarly journals Essential Role of Methionine Residues in Calmodulin Binding toBordetella pertussisAdenylate Cyclase, as Probed by Selective Oxidation and Repair by the Peptide Methionine Sulfoxide Reductases

2004 ◽  
Vol 279 (29) ◽  
pp. 30210-30218 ◽  
Author(s):  
Stéphanie Vougier ◽  
Jean Mary ◽  
Nathalie Dautin ◽  
Joëlle Vinh ◽  
Bertrand Friguet ◽  
...  
Keyword(s):  
Selective Oxidation ◽  
Essential Role ◽  
Methionine Sulfoxide ◽  
Calmodulin Binding ◽  
Methionine Sulfoxide Reductases ◽  
Methionine Residues

scholarly journals In Vivo Effects of Methionine Sulfoxide Reductase Deficiency in Drosophila melanogaster

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 155 ◽  
Author(s):  
Lindsay Bruce ◽  
Diana Singkornrat ◽  
Kelsey Wilson ◽  
William Hausman ◽  
Kelli Robbins ◽  
...  
Keyword(s):  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Model Organisms ◽  
Methionine Sulfoxide Reductase A ◽  
Methionine Sulfoxide Reductases ◽  
Methionine Residues ◽  
Oxidation Of Methionine ◽  
And Function ◽  
In Vivo Effects

The deleterious alteration of protein structure and function due to the oxidation of methionine residues has been studied extensively in age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. Methionine sulfoxide reductases (MSR) have three well-characterized biological functions. The most commonly studied function is the reduction of oxidized methionine residues back into functional methionine thus, often restoring biological function to proteins. Previous studies have successfully overexpressed and silenced MSR activity in numerous model organisms correlating its activity to longevity and oxidative stress. In the present study, we have characterized in vivo effects of MSR deficiency in Drosophila. Interestingly, we found no significant phenotype in animals lacking either methionine sulfoxide reductase A (MSRA) or methionine sulfoxide reductase B (MSRB). However, Drosophila lacking any known MSR activity exhibited a prolonged larval third instar development and a shortened lifespan. These data suggest an essential role of MSR in key biological processes.

scholarly journals Noncatalytic Antioxidant Role forHelicobacter pyloriUrease

2018 ◽  
Vol 200 (17) ◽  
Author(s):  
Alan A. Schmalstig ◽  
Stéphane L. Benoit ◽  
Sandeep K. Misra ◽  
Joshua S. Sharp ◽  
Robert J. Maier
Keyword(s):  
Helicobacter Pylori ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Repair System ◽  
Content Type ◽  
Urease Enzyme ◽  
Catalytic Role ◽  
Methionine Residues ◽  
H Pylori

ABSTRACTThe well-studied catalytic role of urease, the Ni-dependent conversion of urea into carbon dioxide and ammonia, has been shown to protectHelicobacter pyloriagainst the low pH environment of the stomach lumen. We hypothesized that the abundantly expressed urease protein can play another noncatalytic role in combating oxidative stress via Met residue-mediated quenching of harmful oxidants. Three catalytically inactive urease mutant strains were constructed by single substitutions of Ni binding residues. The mutant versions synthesize normal levels of urease, and the altered versions retained all methionine residues. The three site-directed urease mutants were able to better withstand a hypochlorous acid (HOCl) challenge than a ΔureABdeletion strain. The capacity of purified urease to protect whole cells via oxidant quenching was assessed by adding urease enzyme to nongrowing HOCl-exposed cells. No wild-type cells were recovered with oxidant alone, whereas urease addition significantly aided viability. These results suggest that urease can protectH. pyloriagainst oxidative damage and that the protective ability is distinct from the well-characterized catalytic role. To determine the capability of methionine sulfoxide reductase (Msr) to reduce oxidized Met residues in urease, purifiedH. pyloriurease was exposed to HOCl and a previously described Msr peptide repair mixture was added. Of the 25 methionine residues in urease, 11 were subject to both oxidation and to Msr-mediated repair, as identified by mass spectrometry (MS) analysis; therefore, the oxidant-quenchable Met pool comprising urease can be recycled by the Msr repair system. Noncatalytic urease appears to play an important role in oxidant protection.IMPORTANCEChronicHelicobacter pyloriinfection can lead to gastric ulcers and gastric cancers. The enzyme urease contributes to the survival of the bacterium in the harsh environment of the stomach by increasing the local pH. In addition to combating acid,H. pylorimust survive host-produced reactive oxygen species to persist in the gastric mucosa. We describe a cyclic amino acid-based antioxidant role of urease, whereby oxidized methionine residues can be recycled by methionine sulfoxide reductase to again quench oxidants. This work expands our understanding of the role of an already acknowledged pathogen virulence factor and specifically expands our knowledge ofH. pylorisurvival mechanisms.

scholarly journals Role of Methionine Sulfoxide Reductases A and B of Enterococcus faecalis in Oxidative Stress and Virulence

2010 ◽  
Vol 78 (9) ◽  
pp. 3889-3897 ◽  
Author(s):  
Chen Zhao ◽  
Axel Hartke ◽  
Marilena La Sorda ◽  
Brunella Posteraro ◽  
Jean-Marie Laplace ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Enterococcus Faecalis ◽  
Galleria Mellonella ◽  
Methionine Sulfoxide ◽  
Peritoneal Macrophages ◽  
Infection Model ◽  
Repair Enzymes ◽  
Methionine Sulfoxide Reductases ◽  
Mouse Peritoneal Macrophages

ABSTRACT Methionine sulfoxide reductases A and B are antioxidant repair enzymes that reduce the S- and R-diastereomers of methionine sulfoxides back to methionine, respectively. Enterococcus faecalis, an important nosocomial pathogen, has one msrA gene and one msrB gene situated in different parts of the chromosome. Promoters have been mapped and mutants have been constructed in two E. faecalis strains (strains JH2-2 and V583) and characterized. For both backgrounds, the mutants are more sensitive than the wild-type parents to exposure to H2O2, and in combination the mutations seem to be additive. The virulence of the mutants has been analyzed in four different models. Survival of the mutants inside mouse peritoneal macrophages stimulated with recombinant gamma interferon plus lipopolysaccharide but not in naïve phagocytes is significantly affected. The msrA mutant is attenuated in the Galleria mellonella insect model. Deficiency in either Msr enzyme reduced the level of virulence in a systemic and urinary tract infection model. Virulence was reconstituted in the complemented strains. The combined results show that Msr repair enzymes are important for the oxidative stress response, macrophage survival, and persistent infection with E. faecalis.

scholarly journals Methionine Sulfoxide Reduction and Assimilation in Escherichia coli: New Role for the Biotin Sulfoxide Reductase BisC

2005 ◽  
Vol 187 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Benjamin Ezraty ◽  
Julia Bos ◽  
Frédéric Barras ◽  
Laurent Aussel
Keyword(s):  
Escherichia Coli ◽  
Essential Role ◽  
Reductase Activity ◽  
Methionine Sulfoxide ◽  
Mass Spectrometric ◽  
Methionine Sulfoxide Reductase ◽  
Racemic Mixture ◽  
E Coli ◽  
Methionine Sulfoxide Reductases ◽  
Biotin Sulfoxide Reductase

ABSTRACT Methionine ranks among the amino acids most sensitive to oxidation, which converts it to a racemic mixture of methionine-S-sulfoxide (Met-S-SO) and methionine-R-sulfoxide (Met-R-SO). The methionine sulfoxide reductases MsrA and MsrB reduce free and protein-bound MetSO, MsrA being specific for Met-S-SO and MsrB for Met-R-SO. In the present study, we report that an Escherichia coli metB1 auxotroph lacking both msrA and msrB is still able to use either of the two MetSO enantiomers. This indicates that additional methionine sulfoxide reductase activities occur in E. coli. BisC, a poorly characterized biotin sulfoxide reductase, was identified as one of these new methionine sulfoxide reductases. BisC was purified and found to exhibit reductase activity with free Met-S-SO but not with free Met-R-SO as a substrate. Moreover, a metB1 msrA msrB bisC strain of E. coli was unable to use Met-S-SO for growth, but it retained the ability to use Met-R-SO. Mass spectrometric analyses indicated that BisC is unable to reduce protein-bound Met-S-SO. Hence, this study shows that BisC has an essential role in assimilation of oxidized methionines. Moreover, this work provides the first example of an enzyme that reduces free MetSO while having no activity on peptide-bound MetSO residues.

scholarly journals Redox controls RecA protein activity via reversible oxidation of its methionine residues

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Camille Henry ◽  
Laurent Loiseau ◽  
Alexandra Vergnes ◽  
Didier Vertommen ◽  
Angela Mérida-Floriano ◽  
...  
Keyword(s):  
Dna Recombination ◽  
Reca Protein ◽  
Methionine Sulfoxide ◽  
Mass Spectrometry Analysis ◽  
Loss Of Function ◽  
Protein Activity ◽  
Spectrometry Analysis ◽  
Methionine Sulfoxide Reductases ◽  
Methionine Residues ◽  
Biochemical Analyses

Reactive oxygen species (ROS) cause damage to DNA and proteins. Here we report that the RecA recombinase is itself oxidized by ROS. Genetic and biochemical analyses revealed that oxidation of RecA altered its DNA repair and DNA recombination activities. Mass spectrometry analysis showed that exposure to ROS converted 4 out of 9 Met residues of RecA to methionine sulfoxide. Mimicking oxidation of Met35 by changing it for Gln caused complete loss of function whereas mimicking oxidation of Met164 resulted in constitutive SOS activation and loss of recombination activity. Yet, all ROS-induced alterations of RecA activity were suppressed by methionine sulfoxide reductases MsrA and MsrB. These findings indicate that under oxidative stress, MsrA/B is needed for RecA homeostasis control. The implication is that, besides damaging DNA structure directly, ROS prevent repair of DNA damage by hampering RecA activity.

scholarly journals Gene Expression and Physiological Role of Pseudomonas aeruginosa Methionine Sulfoxide Reductases during Oxidative Stress

2013 ◽  
Vol 195 (15) ◽  
pp. 3299-3308 ◽  
Author(s):  
A. Romsang ◽  
S. Atichartpongkul ◽  
W. Trinachartvanit ◽  
P. Vattanaviboon ◽  
S. Mongkolsuk
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Physiological Role ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductases

scholarly journals Role of Helicobacter pylori methionine sulfoxide reductase in urease maturation

2013 ◽  
Vol 450 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Lisa G. Kuhns ◽  
Manish Mahawar ◽  
Joshua S. Sharp ◽  
Stéphane Benoit ◽  
Robert J. Maier
Keyword(s):  
Helicobacter Pylori ◽  
Parent Strain ◽  
Specific Activity ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Accessory Proteins ◽  
Wild Type ◽  
Methionine Residues ◽  
H Pylori

The persistence of the gastric pathogen Helicobacter pylori is due in part to urease and Msr (methionine sulfoxide reductase). Upon exposure to relatively mild (21% partial pressure of O2) oxidative stress, a Δmsr mutant showed both decreased urease specific activity in cell-free extracts and decreased nickel associated with the partially purified urease fraction as compared with the parent strain, yet urease apoprotein levels were the same for the Δmsr and wild-type extracts. Urease activity of the Δmsr mutant was not significantly different from the wild-type upon non-stress microaerobic incubation of strains. Urease maturation occurs through nickel mobilization via a suite of known accessory proteins, one being the GTPase UreG. Treatment of UreG with H2O2 resulted in oxidation of MS-identified methionine residues and loss of up to 70% of its GTPase activity. Incubation of pure H2O2-treated UreG with Msr led to reductive repair of nine methionine residues and recovery of up to full enzyme activity. Binding of Msr to both oxidized and non-oxidized UreG was observed by cross-linking. Therefore we conclude Msr aids the survival of H. pylori in part by ensuring continual UreG-mediated urease maturation under stress conditions.

scholarly journals Methionine Redox Homeostasis in Protein Quality Control

2021 ◽  
Vol 8 ◽  
Author(s):  
Laurent Aussel ◽  
Benjamin Ezraty
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Protein Function ◽  
Protein Quality ◽  
Redox Homeostasis ◽  
Protein Quality Control ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductases ◽  
Methionine Residues ◽  
And Function

Bacteria live in different environments and are subject to a wide variety of fluctuating conditions. During evolution, they acquired sophisticated systems dedicated to maintaining protein structure and function, especially during oxidative stress. Under such conditions, methionine residues are converted into methionine sulfoxide (Met-O) which can alter protein function. In this review, we focus on the role in protein quality control of methionine sulfoxide reductases (Msr) which repair oxidatively protein-bound Met-O. We discuss our current understanding of the importance of Msr systems in rescuing protein function under oxidative stress and their ability to work in coordination with chaperone networks. Moreover, we highlight that bacterial chaperones, like GroEL or SurA, are also targeted by oxidative stress and under the surveillance of Msr. Therefore, integration of methionine redox homeostasis in protein quality control during oxidative stress gives a complete picture of this bacterial adaptive mechanism.

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