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

Ranaivoson, F.M.; Antoine, Mathias; Kauffmann, Brice; Boschi‐Muller, Sandrine; Aubry, A.; Branlant, Guy; Favier, F.

doi:10.1016/j.jmb.2008.01.021

Cited by 39 publications

(42 citation statements)

References 27 publications

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“…4A). These stabilization interactions were also observed in the x-ray structure of N. meningitidis MsrA bound to Ac-Met-S-SO-NHMe (27) (Fig. 4C).…”

Section: Discussionsupporting

confidence: 65%

“…With these interactions, the cacodylate mimics the L-Met-SO substrate; the oxygen atom of the cacodylate is located at the position of the sulfoxide oxygen of the Met-SO, and the two methyl groups of cacodylate are directed toward the hydrophobic pocket, as is the ⑀-methyl of Met-SO, as can be seen in the structure of Neisseria meningitidis MsrA bound to Ac-Met-S-SO-NHMe (Fig. 4C) (27).…”

Section: A Cacodylate Molecule In the Active Site Mimics The L-met-somentioning

confidence: 86%

“…4, A and B). X-ray and NMR studies on E. coli and N. meningitidis MsrA showed that the formation of the first disulfide bond in the thiol disulfide relay mechanism requires large conformational flexibilities (27,28,30). Obtaining a crystal structure of fully reduced and/or oxidized Cd-MsrA would be required to assess whether this conformational change is also required for Cd-MsrA.…”

Section: Discussionmentioning

confidence: 99%

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Corynebacterium diphtheriae Methionine Sulfoxide Reductase A Exploits a Unique Mycothiol Redox Relay Mechanism

Tossounian

Pedre

Wahni

et al. 2015

Journal of Biological Chemistry

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Background: Methionine sulfoxide post-translational modifications have an important new signaling role in cells. Results: Methionine sulfoxide reductase MsrA of the pathogenic actinomycete Corynebacterium diphtheriae (Cd-MsrA) uses a unique intramolecular redox relay mechanism coupled to mycothiol. Conclusion: For methionine sulfoxide control, Cd-MsrA is flexible in receiving electrons from both the thioredoxin and the mycothiol pathways. Significance: C. diphtheriae MsrA is a redox regulator for methionine sulfoxide signaling.

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“…4A). These stabilization interactions were also observed in the x-ray structure of N. meningitidis MsrA bound to Ac-Met-S-SO-NHMe (27) (Fig. 4C).…”

Section: Discussionsupporting

confidence: 65%

Section: A Cacodylate Molecule In the Active Site Mimics The L-met-somentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Corynebacterium diphtheriae Methionine Sulfoxide Reductase A Exploits a Unique Mycothiol Redox Relay Mechanism

Tossounian

Pedre

Wahni

et al. 2015

Journal of Biological Chemistry

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“…In the scenario, a sulfurane intermediate/transition state is formed that rearranges into a sulfenic acid intermediate (see Scheme 1A). Therefore, Asp 143 and Wat 99 should interact not only with the oxygen of the sulfoxide and its polarized form but probably also with the OH of the sulfurane transition state and directly or indirectly with the OH of the sulfenic acid, as observed in the crystal structure of the MsrA sulfenic acid intermediate (22). To form a sulfurane, the Cys 118 has to be under the thiolate form to attack the sulfur of the sulfoxide, the geometry of which is tetrahedral.…”

Section: Discussionmentioning

confidence: 99%

Structural and Biochemical Characterization of Free Methionine-R-sulfoxide Reductase from Neisseria meningitidis

Gruez¹,

Libiad²,

Boschi‐Muller

et al. 2010

Journal of Biological Chemistry

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Methionine (Met) 4 is one of the two amino acids in proteins that are the most susceptible to oxidation by reactive oxygen species, forming Met-O (1). Prior to 2007, two families of methionine-sulfoxide reductase (Msr) enzymes, called MsrA and -B were known to reduce Met-O back into Met (2, 3). The MsrA family reduces the S isomer at the sulfoxide function, whereas MsrB is specific for the R isomer. Both Msrs, which reveal distinct unrelated folds, were shown to reduce more efficiently a Met-O within a polypeptide chain. Therefore, Msrs are repair enzymes that play important roles in the protection of cells against oxidative stress (3-5).The catalytic mechanism of MsrA and MsrB is now well documented. For most MsrAs and MsrBs (i.e. those possessing a recycling Cys), the mechanism comprises three steps: a reductase step that leads to formation of a sulfenic acid intermediate on a catalytic Cys (6), a second step in which a disulfide bond is formed between the catalytic Cys and a recycling Cys, and finally, a step in which the intradisulfide bond is reduced by thioredoxin (Trx) or a Trx-like protein (7). A catalytic residue (i.e. Glu 94 in MsrA and His 103 in MsrB) was characterized, one of whose major roles is to protonate the oxygen of the sulfoxide function (8, 9). In all of the MsrAs and MsrBs studied to date, the reduction of the disulfide bond is rate-limiting, whereas the formation of the sulfenic acid intermediate is rate-determining in the process leading to intradisulfide bond formation. In other words, in the absence of Trx, only the intradisulfide intermediate accumulates.Recently, a third family of Msr, named fRMsr, was discovered (10). The fRMsrs exhibit a GAF-type fold. GAF domains are one of the largest and most widespread domains found in all kingdoms of life. They are dimeric and are generally arranged in tandem in modular proteins to provide a large variety of regulation functions. However, most of the functions of GAF domains remain to be studied in detail. The fRMsr is the first case of a GAF domain that bears a catalytic activity. The fRMsrs are present in eubacteria and unicellular eukaryotes (11). The family displays a methionine-sulfoxide reductase activity, reducing selectively free Met-O with an R configuration at the sulfoxide (10). Such a function led Lowther and co-workers (10) to propose that Met-R-O can represent a signaling molecule in response to oxidative stress.Only the crystal structures of fRMsr from Escherichia coli and Saccharomyces cerevisiae have been solved to date, without substrate (12, 13). Both structures are described as being composed of six ␤-strands, four ␣-helices, and two prominent loops, loop 1 and loop 2, located on the surface of the protein * This work was supported by the CNRS, the University of Nancy I, and the IFR ; E-mail: Guy.Branlant@maem.uhp-nancy.fr. 4 The abbreviations used are: Met, methionine; Met-O, methionine sulfoxide (DL-Met-R,S-O); MES, 2-(N-morpholino)ethanesulfonic acid; 2-PDS, 2,2Ј-dithiodipyridine; DTNB, 5,5Ј-dithiobis(2-nitro)benzoate; ...

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“…In the final step, the disulfide bridge is reduced by an electron donor, the NADPHdependent thioredoxin/TR system, leading to the regeneration of the Msr active site. The catalytic mechanism varies between different Msrs, especially in the number of recycling cysteines [49,50] . However, the selenoprotein MsrB1 is believed to use an alternative recycling cysteine residue located in a different position [28] .…”

Section: Catalytic Mechanism Of Msrsmentioning

confidence: 99%

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

Sreekumar¹

2011

WJBC

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Methionine is a highly susceptible amino acid that can be oxidized to S and R diastereomeric forms of methionine sulfoxide by many of the reactive oxygen species generated in biological systems. Methionine sulfoxide reductases (Msrs) are thioredoxin-linked enzymes involved in the enzymatic conversion of methionine sulfoxide to methionine. Although MsrA and MsrB have the same function of methionine reduction, they differ in substrate specificity, active site composition, subcellular localization, and evolution. MsrA has been localized in different ocular regions and is abundantly expressed in the retina and in retinal pigment epithelial (RPE) cells. MsrA protects cells from oxidative stress. Overexpression of MsrA increases resistance to cell death, while silencing or knocking down MsrA decreases cell survival; events that are mediated by mitochondria. MsrA participates in protein-protein interaction with several other cellular proteins. The interaction of MsrA with α-crystallins is of utmost importance given the known functions of the latter in protein folding, neuroprotection, and cell survival. Oxidation of methionine residues in α-crystallins results in loss of chaperone function and possibly its antiapoptotic properties. Recent work from our laboratory has shown that MsrA is co-localized with αA and αB crystallins in the retinal samples of patients with age-related macular degeneration. We have also found that chemically induced hypoxia regulates the expression of MsrA and MsrB2 in human RPE cells. Thus, MsrA is a critical enzyme that participates in cell and tissue protection, and its interaction with other proteins/growth factors may provide a target for therapeutic strategies to prevent degenerative diseases.

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

Cited by 39 publications

References 27 publications

Corynebacterium diphtheriae Methionine Sulfoxide Reductase A Exploits a Unique Mycothiol Redox Relay Mechanism

Corynebacterium diphtheriae Methionine Sulfoxide Reductase A Exploits a Unique Mycothiol Redox Relay Mechanism

Structural and Biochemical Characterization of Free Methionine-R-sulfoxide Reductase from Neisseria meningitidis

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

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