Review
Methionine sulfoxide reductases in prokaryotes

https://doi.org/10.1016/j.bbapap.2004.08.017Get rights and content

Abstract

In living organisms, most methionine residues exposed to reactive oxygen species (ROS) are converted to methionine sulfoxides. This reaction can lead to structural modifications and/or inactivation of proteins. Recent years have brought a wealth of new information on methionine sulfoxide reductase A (MsrA) and B (MsrB) which makes methionine oxidation a reversible process. Homologs of msrA and msrB genes have been identified in most living organisms and their evolution throughout different species led to different genetic organization and different copy number per organism. While MsrA and MsrB had been the focus of multiple biochemical investigations, our understanding of their physiological role in vivo remains scarce. Yet, the recent identification of a direct link between protein targeting and MsrA/MsrB repair offers a best illustration of the physiological importance of this pathway. Repeatedly identified as a potential “virulence factor”, contribution of msrA to pathogenicity is also discussed. It remains, however, unclear whether reduced virulence results from overall viability loss or relates to specific oxidized virulence factors left unrepaired. We speculate that a major issue towards assessing the in vivo role of the MsrA/MsrB repair pathway in the next future will be to decipher the interrelations, if any, between MsrA/MsrB-mediated repair and chaperone-assisted folding and/or protease-assisted degradation.

Introduction

Oxidative stress results from an imbalance between production of reactive oxygen species (ROS) and their elimination, with the eventual consequences of their action being detrimental for the cells [1]. ROS originate from monoelectronic reduction of O2 [2]. ROS is a generic term that includes radical species such as superoxide anion (O2radical dot) and hydroxyl radical (HOradical dot) as well as other potentially harmful oxygen derivatives, such as hydrogen peroxide (H2O2) or singlet oxygen (1O2). All of these ROS exhibit different half-lifes and diffusion rates and can be interconverted by metal- or enzymatic assisted catalysis. Most macromolecules (nucleic acids, proteins, lipids) constitute targets for ROS and consequences are in most cases functional alteration [3]. Sugars and free amino acids can also be oxidized thereby loosing their biological value as nutrients.

A series of anti-oxidant devices have been selected throughout evolution. The best studied cases are enzymes that eliminate ROS prior to damage occurrence; this includes superoxide dismutase, catalase, alkylhydroxyperoxidases, and heme oxygenase [4]. Another strategy is based on the use of small compounds that sequester ROS such as glutathione, vitamins or ubiquinone, to name a few [5]. Despite these antioxidant barriers, damage can occur and a third type of strategy is to repair the damaged molecule. While DNA repair has been well studied, analysis of protein repair pathways is much less known. Methionine sulfoxide reductase activity (Msr) provides a typical case of post-damages enzymes repairing proteins.

Section snippets

Biochemical aspects of methionine oxido-reduction

Methionine (Met) ranks among the amino acids as the most sensitive to oxidation that converts it into methionine sulfoxide (MetSO). Actually, oxidation produces two diastereoisomers of MetSO, referred to as Met-(S)-SO and Met-(R)-SO, owing to the asymmetric position of the sulfur atom in the lateral chain (Fig. 1). Reversion of MetSO to Met is catalyzed by MsrA and MsrB which are specific for the S and R diastereoisomer forms, respectively [6], [7]. MsrA and MsrB can act on both free and

Genetic and evolutionary aspects of msrA and msrB genes

A most striking feature of Msr biology is that MsrA and MsrB enzymes share homology neither at the primary sequence nor at the structural levels [9], [10]. Their close relatedness, from the catalytic mechanism used to their role in the overall cell physiology, makes a compelling case of convergent evolution.

Orthologs to msrA and msrB genes are present in most genomes available [11]. However, quite a great variety is to be found when considering genetic organization (Fig. 2). In numerous

Genetic organization

The msrA and msrB genes of E. coli are located at 95.69 and 40.09 min on the chromosome. The E. coli msrA gene was cloned and expressed for the first time in 1992 [15]. Since MsrA was specific of the S diastereoisomer, the existence of an epimerase was postulated to account for the reduction of the R diastereoisomer. In 2001, discovery of a MsrB activity, hence of a second methionine sulfoxide reductase, was obtained in studies of E. coli when it was realized that orthologs to yeaA, an ORF of

Importance of msrA and msrB genes in bacterial pathogenicity

In the recent years, MsrA emerged as a virulence determinant in numerous pathogens. Hereafter are reported selected cases of involvement of msr genes in virulence. These examples provide useful information on the role of msrA and msrB genes in organisms exposed to diverse natural niches.

Role of MsrA/MsrB repair pathway in cellular protein dynamic

It is remarkable that despite the occurrence of numerous antioxidant systems in most bacteria, the absence of MsrA/MsrB almost invariably leads to increased susceptibility to oxidative agents. A first hypothesis is that there are a few essential process, the required efficiency of which is altered by methionine oxidation, and the MsrA/MsrB dependent repair of which is crucial for cell life. Identification of SRP, an essential targeting cellular machinery, might constitute one of these cases. A

Concluding comments

Based on numerous biochemical investigations carried out in the nineties, the recent decade has seen a flourishing development of Msr biology. Various reasons underlie this increased interest in these biological activities among which a remarkable conservation throughout all living organisms, the emergence of oxidative stress as a biological phenomenon of paramount importance in basic, medical and applied sciences and the novelty of the protein repair concept. As for many other process pivotal

Acknowledgements

Thanks are due to the FB group and to P. Moreau for fruitful discussion. This work was supported by grants from the Université Aix-Marseille II, from CNRS (Programme PICS 1579), and from Fondation pour la Recherche Médicale.

References (45)

  • G.C. Melkani et al.

    Hydrogen peroxide induces the dissociation of GroEL into monomers that can facilitate the reactivation of oxidatively inactivated rhodanese

    Int. J. Biochem. Cell Biol.

    (2004)
  • H.K. Khor et al.

    Potential role of methionine sulfoxide in the inactivation of the chaperone GroEL by hypochlorous acid (HOCl) and peroxynitrite (ONOO)

    J. Biol. Chem.

    (2004)
  • A. Abulimiti et al.

    Reversible methionine sulfoxidation of Mycobacterium tuberculosis small heat shock protein Hsp16.3 and its possible role in scavenging oxidants

    Biochem. Biophys. Res. Commun.

    (2003)
  • D. Harman

    Aging: a theory based on free radical and radiation chemistry

    J. Gerontol.

    (1956)
  • J.A. Imlay

    Pathways of oxidative damage

    Annu. Rev. Microbiol.

    (2003)
  • E. Cabiscol et al.

    Oxidative stress in bacteria and protein damage by reactive oxygen species

    Int. Microbiol.

    (2000)
  • B. Kauffmann et al.

    Crystallization and preliminary X-ray diffraction studies of the peptide methionine sulfoxide reductase B domain of Neisseria meningitidis PILB

    Acta Crystallogr.

    (2002)
  • W.T. Lowther et al.

    The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB

    Nat. Struct. Biol.

    (2002)
  • G.V. Kryukov et al.

    Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase

    Proc. Natl. Acad. Sci. U. S. A.

    (2002)
  • V.K. Singh et al.

    Multiple methionine sulfoxide reductase genes in Staphylococcus aureus: expression of activity and roles in tolerance of oxidative stress

    Microbiology

    (2003)
  • M.J. Rodrigo et al.

    Reverse genetic approaches in plants and yeast suggest a role for novel, evolutionarily conserved, selenoprotein-related genes in oxidative stress defense

    Mol. Genet. Genomics

    (2002)
  • M. Zhang et al.

    Molecular mechanisms of calmodulin's functional versatility

    Biochem. Cell. Biol.

    (1998)
  • Cited by (0)

    a

    Present address: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA

    View full text