Methionine sulfoxide reductase

MsrA, thioredoxin-dependent peptide methionine sulfoxide reductase... 

Boschi-Mueller S., Azza S., Sanglier-Cianferani S., Talfoumier F., Van Dorsselear A., and Barnalnt G. (2000), A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of methionine sulfoxide reductase from E.coli, J. Biol. Chem. 275, 35908-35913. 

Moskovitz J., Flescher E., Berlett B.S., Azare J., Poston J.M., and Stadtman E.R. (1998), Overexpression of peptide-methionine sulfoxide reductase in Saccharomy-ces cerevisiae and human T cells provides them with high resistance to oxidative stress, Proc. Nat. Acad. Sci. U.S.A. 95, 14071-14075. 

The stem-loop structure in the noncoding 3 region of selenoprotein mRNAs has also been termed a SECTS element in mammals although it has a different overall structure. ° In silica analysis of the human genome sequence, using this consensus SECTS element along with the presence of the characteristic UGA codon within an exon, has led to the discovery of several new selenoproteins, including a selenium-dependent methionine sulfoxide reductase. It has been shown that a specific complex exists for selenoprotein synthesis that shuttles between the nucleus and the cytosol. This possibly protects the preformed complex for nonsense-mediated decay to allow for more efficient selenoprotein synthesis. The specific tRNA needed for selenocysteine... 

METHIONINE ADENOSYLTRANSFERASE METHIONINE y-LYASE METHIONINE SULFOXIDE REDUCTASE Methionine synthase,... 

PEPTIDOMIMETIC COMPOUND PEPTIDE METHIONINE SULFOXIDE REDUCTASE... 

Some mutant mice have extended lifespans. The Ames dwarf mouse has a mutation in p66shc, a cell-surface protein that contains both Src-homology and collagen-homology domains. It lives almost one-third longer than do wild-type mice.538 Mice deficient in methionine sulfoxide reductase have a reduced lifespan539 but fruit flies with overexpressed activity of the enzyme are more resistant than wild-type flies to oxidative damage.540... 

Methionine sulfoxide formation may occur without noticeable changes in physical or immunochemical properties of the protein. Thus reduction of sulfoxide to thioether often completely restores the lost protein function. Many cells, including human polymoprhonuclear neutrophilic leukocytes, contain enzyme methionine sulfoxide reductase, which is able to convert methionine sulfoxide to the reduced methione form in a variety of proteins (B25, F8). Methionine reacting with a strong oxidant effects methionine sulfone production, which in vivo is not reduced back to methionine. 

The repair of oxidative damage may be incomplete. Only reduction of the d-diastereomer of calmodulin-bound methionine sulfoxide (L-Met-D-SO) by methionine sulfoxide reductase was demonstrated, while in the cells both d- and l-steoreoisomers are formed. Such incomplete, diastereoselective repair by methionine sulfoxide reductase contributes to the accumulation of methionine sulfoxide residues during oxidative stress and aging in vivo (S24). 

Sharov, V. S., Ferrington, D. A., Squier, T. C., and Schoneich, C., Diastereoselective reduction of protein-bound methionine sulfoxide by methionine sulfoxide reductase. FEBS Lett. 455, 247-250(1999). 

Qabbita SP, Aksenov MY, LoveU MA, Markesbery WR (1999) Decrease in peptide methionine sulfoxide reductase in Alzheimer s disease brain. J Neurochem 73 1660-1666 Geddes JW, Pang Z, Wiley DH (1996) Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism. Implications for Alzheimer disease. Mol Chem Neuropathol 28 65-74... 

Mammalia contain two methionine sulfoxide reductases, forms A and B. Methionine sulfoxide reductase B is a selenoprotein, which reduces the R form of free or protein-bound methionine sulfoxides to methionine with thioredoxin as the reductant. Together with isoform A (which does not contain selenium), the enzyme can repair oxidatively damaged protein and thus contributes to the antioxidant system of the cell. ... 

A question of particular interest concerns the catalytic advantage that a selenol in the active site of an enzyme has in comparison to a thiol group. It has been approached by replacing the selenocysteine in the formate dehydrogenase Ft by a cysteine residue and by determining the catalytic parameters of the Se-wild-type species with the mutant S-species. Table 1 presents the data obtained. They show that koit of the Se enzyme is more than 300-fold higher than that of the S variant and that the affinity to the substrate is only marginally affected. Similar replacements of selenocysteine by cysteine in other enzymes like the deiodinase type 1 or methionine sulfoxide reductase B corroborated these results. 

Moreover, formation of radical transients with S.-.O bonds is kinetically preferred, but on longer time scale they convert into transients with S.-.N bonds in a pH dependent manner. Ultimately transients with S.-.N bonds transform intramolecularly into C-centred radicals located on the C moiety of the peptide backbone. Another type of C-centred radicals located in the side chain of Met-residue, a-(aikylthio)alkyl radicals, are formed via deprotonation of MetS +. C-centred radicals are precursors for peroxyl radicals (ROO ) that might be involved in chain reactions of peptide and/or protein oxidation. Stabilization of MetS +through formation of S.-.O- and S.-.N-bonded radicals might potentially accelerate oxidation and autooxidation processes of Met in peptides and proteins. Considering that methionine sulfoxide, which is the final product coming from all radicals centred on sulphur, is restored by the enzyme methionine sulfoxide reductase into MetS, stabilization of MetS +appears as a protection against an eventual peroxidation chain that would develop from a carbon centred radical. 

Besides thiol repair there also exists direct repair for one of the oxidation products of methionine, methionine sulfoxide. The enzyme peptide methionine sulfoxide reductase reduces the methionine sulfoxide formed in proteins due to oxidation and is therefore able to reconstitute the normal protein (Fig. 3). Besides methionine sulfoxide there exists a further oxidation product of methionine, methionine sulfone, which can not be repaired. The cycle of methionine oxidation and efficient methionine sulfoxide repair, and the early and easy oxidation of the methionine in proteins, led some authors to hypothesize that methionine acts as an intramolecular antioxidant for some proteins and so protects other amino acids from oxidation [12]. Besides the peptide methionine sulfoxide reductases, there also exists methionine reductases able to... 

Etienne, F., Resnick, L., Sagher, D., Brot, N., and Weissbach, H. (2003) Reduction of sulindac to its active metabolite, sulindac sulfide assay and role of the methionine sulfoxide reductase system. Biochem. Biophys. Res. Commun. 312, 1005-1010. 

Kryukov GV, Kumae RA, Koc A, Sun Z and Gladyshev VN (2002) Selenoprotein R is a zinc-containing stereospecific methionine sulfoxide reductase. Proc Natl Acad Sci USA 99 4245-4250. 

GUSTAVSSON, N., KOKKE, B.P., HARNDAHL, U., SILOW, M., BECHTOLD, U., POGHOSYAN, Z., MURPHY, D., BOELENS, W.C., SUNDBY, C., A peptide methionine sulfoxide reductase highly expressed in photosynthetic tissue in Arabidopsis thaliana can protect the chaperone-like activity of a chloroplast-localized small heat shock protein., Plant J.. 2002, 29, 545-553. 

MCD spectroscopy has been used to probe the excited state electronic structure of the electron transfer relevant [Mo -OH][Fe ] state of chicken SO and the Mo(v) resting state of YedY. YedY(MsrPQ) possesses the SUOX fold, and has recently been shown to be a periplasmic methionine sulfoxide reductase. Protein film voltammetry has been used to propose a mechanism for... 

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