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Information on EC 1.8.4.11 - peptide-methionine (S)-S-oxide reductase and Organism(s) Rattus norvegicus and UniProt Accession Q923M1

for references in articles please use BRENDA:EC1.8.4.11
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IUBMB Comments
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for the reduction of the S-form of L-methionine S-oxide, acting faster on the residue in a peptide than on the free amino acid . On the free amino acid, it can also reduce D-methionine (S)-S-oxide but more slowly . The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.12, peptide-methionine (R)-S-oxide reductase, are found within the same protein whereas, in other species, they are separate proteins [1,4]. The reaction proceeds via a sulfenic-acid intermediate [5,10].
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Rattus norvegicus
UNIPROT: Q923M1
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The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
methionine sulfoxide reductase a, msra1, msra2, methionine sulfoxide reductases a, msra-1, methionine-s-sulfoxide reductase, peptide methionine sulphoxide reductase, methionine sulphoxide reductase a, peptide methionine sulfoxide reductase a, protein-methionine-s-oxide reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methionine sulfoxide reductase A
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methionine sulphoxide reductase A
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methionine S-oxide reductase (S-form oxidizing)
-
-
-
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methionine sulfoxide reductase
-
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methionine sulphoxide reductase A
-
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peptide methionine sulfoxide reductase
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SYSTEMATIC NAME
IUBMB Comments
peptide-L-methionine:thioredoxin-disulfide S-oxidoreductase [L-methionine (S)-S-oxide-forming]
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for the reduction of the S-form of L-methionine S-oxide, acting faster on the residue in a peptide than on the free amino acid [9]. On the free amino acid, it can also reduce D-methionine (S)-S-oxide but more slowly [9]. The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.12, peptide-methionine (R)-S-oxide reductase, are found within the same protein whereas, in other species, they are separate proteins [1,4]. The reaction proceeds via a sulfenic-acid intermediate [5,10].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
N-acetyl-L-methionine (S)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
?
calmodulin L-methionine-(S)-sulfoxide + thioredoxin
calmodulin L-methionine + thioredoxin disulfide
show the reaction diagram
dabsyl-L-methionine (S)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
synthetic substrate
-
-
?
dimethylsulfide + thioredoxin disulfide + H2O
dimethylsulfoxide + thioredoxin
show the reaction diagram
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA is specific for the S-form
-
-
?
protein-L-methionine (S)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
-
cellular system of balancing native proteins and oxidatively damaged proteins by use of protein biosynthesis, protein oxidative modification, protein elimination, and oxidized protein repair involving the enzyme, overview, enzyme protects against oxidative damage of proteins, loss of enzyme activity is age-related
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
calmodulin L-methionine-(S)-sulfoxide + thioredoxin
calmodulin L-methionine + thioredoxin disulfide
show the reaction diagram
-
MsrA is specific for the S-form, enzyme provides protection against oxidative damage by reactive oxygen species and has a repair function for oxidized protein methionine residues, which restores the calmodulin binding to adenylate cyclase of the pathogen Bordetella pertussis, which is an essential step for the bacterium to enter host cells, overview
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA is specific for the S-form
-
-
?
protein-L-methionine (S)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA is specific for the S-form, enzyme provides protection against oxidative damage by reactive oxygen species and has a repair function for oxidized protein methionine residues
-
-
?
additional information
?
-
-
cellular system of balancing native proteins and oxidatively damaged proteins by use of protein biosynthesis, protein oxidative modification, protein elimination, and oxidized protein repair involving the enzyme, overview, enzyme protects against oxidative damage of proteins, loss of enzyme activity is age-related
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
H2O2
the enzyme is only inactivated by high doses of H2O2, when treated with 0.5 mM H2O2 MsrA loses 20% of its activity and this inhibition reaches approximately 40% with 1 mM H2O2, MsrA is not significantly inhibited by lower concentrations of H2O2 (0.050 and 0.1 mM)
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0002
-
cytosol, overall Msr activity, substrate is a mixture of S- and R-form of dabsyl L-methionine sulfoxide
0.00021
-
mitochondria, overall Msr activity, substrate is a mixture of S- and R-form of dabsyl L-methionine sulfoxide
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
Manually annotated by BRENDA team
splice variant msrA2a. Multiple MSRA variants participate in the repair of oxidized proteins in vascular smooth muscle cells mitochondria
Manually annotated by BRENDA team
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retinal pigment epithelium
Manually annotated by BRENDA team
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retinal pigment epithelium
Manually annotated by BRENDA team
additional information
-
organ-specific expression patterns
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
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astragaloside IV protects PC-12 cells from 1-methyl-4-phenylpyridinium-induced oxidative damage through upregulating MsrA. Astragaloside IV may serve as an effective therapeutic agent for aging and Parkinson's disease
metabolism
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MsrA expression is dependent on the Sirt1-FOXO3a signaling pathway
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MSRA_RAT
233
0
25851
Swiss-Prot
Mitochondrion (Reliability: 2)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
enzyme precursor contains a cleavable N-terminal signal sequence for targeting to the mitochondria
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
MsrA from cytosolic and mitochondrial fractions
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recombinant MsrA from Escherichia coli strain BL21(DE3)
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
expression of MsrA in Escherichia coli strain BL21(DE3)
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mitochondrial and cytosolic isozymes are encoded by a single gene
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mitochondrial and cytosolic isozymes are encoded on a single gene with 2 initiations sites, delivering an N-terminal signal peptide to the mitochondrial enzyme form
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
astragaloside IV protects PC-12 cells from 1-methyl-4-phenylpyridinium-induced oxidative damage through upregulating MsrA. MsrA expression is dependent on the Sirt1-FOXO3a signaling pathway
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oxidative stress reduces the expression of the enzyme (MsrA) following treatment with 1-methyl-4-phenylpyridinium
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
rapid and specific microplate assay to monitor MsrA activity based on oxidation of dithiothreitol, whose color can be produced by reacting with Ellman's reagent
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vougier, S.; Mary, J.; Friguet, B.
Subcellular localization of methionine sulphoxide reductase A (MsrA): evidence for mitochondrial and cytosolic isoforms in rat liver cells
Biochem. J.
373
531-537
2003
Rattus norvegicus
Manually annotated by BRENDA team
Petropoulos, I.; Friguet, B.
Protein maintenance in aging and replicative senescence: a role for the peptide methionine sulfoxide reductases
Biochim. Biophys. Acta
1703
261-266
2005
Saccharomyces cerevisiae, Drosophila melanogaster, Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Vougier, S.; Mary, J.; Dautin, N.; Vinh, J.; Friguet, B.; Ladant, D.
Essential role of methionine residues in calmodulin binding to Bordetelle pertussis adenylate cyclase, as probed by selective oxidation and repair by the peptide methionine sulfoxide reductases
J. Biol. Chem.
279
30210-30218
2004
Rattus norvegicus
Manually annotated by BRENDA team
Picot, C.R.; Moreau, M.; Juan, M.; Noblesse, E.; Nizard, C.; Petropoulos, I.; Friguet, B.
Impairment of methionine sulfoxide reductase during UV irradiation and photoaging
Exp. Gerontol.
42
859-863
2007
Mus musculus, Rattus norvegicus, Homo sapiens (Q9UJ68), Homo sapiens
Manually annotated by BRENDA team
Haenold, R.; Wassef, R.; Hansel, A.; Heinemann, S.H.; Hoshi, T.
Identification of a new functional splice variant of the enzyme methionine sulphoxide reductase A (MSRA) expressed in rat vascular smooth muscle cells
Free Radic. Res.
41
1233-1245
2007
Rattus norvegicus (Q923M1)
Manually annotated by BRENDA team
Le, H.T.; Chaffotte, A.F.; Demey-Thomas, E.; Vinh, J.; Friguet, B.; Mary, J.
Impact of hydrogen peroxide on the activity, structure, and conformational stability of the oxidized protein repair enzyme methionine sulfoxide reductase A
J. Mol. Biol.
393
58-66
2009
Rattus norvegicus (Q923M1)
Manually annotated by BRENDA team
Guan, X.L.; Wu, P.F.; Wang, S.; Zhang, J.J.; Shen, Z.C.; Luo, H.; Chen, H.; Long, L.H.; Chen, J.G.; Wang, F.
Dimethyl sulfide protects against oxidative stress and extends lifespan via a methionine sulfoxide reductase A-dependent catalytic mechanism
Aging Cell
16
226-236
2017
Drosophila melanogaster, Rattus norvegicus, Caenorhabditis elegans (O02089)
Manually annotated by BRENDA team
Wu, P.; Zhang, Z.; Guan, X.; Li, Y.; Zeng, J.; Zhang, J.; Long, L.; Hu, Z.; Wang, F.; Chen, J.
A specific and rapid colorimetric method to monitor the activity of methionine sulfoxide reductase A
Enzyme Microb. Technol.
53
391-397
2013
Rattus norvegicus (Q923M1)
Manually annotated by BRENDA team
Dun, Y.; Vargas, J.; Brot, N.; Finnemann, S.C.
Independent roles of methionine sulfoxide reductase A in mitochondrial ATP synthesis and as antioxidant in retinal pigment epithelial cells
Free Radic. Biol. Med.
65
1340-1351
2013
Rattus norvegicus
Manually annotated by BRENDA team
Lourenco Dos Santos, S.; Petropoulos, I.; Friguet, B.
The oxidized protein repair enzymes methionine sulfoxide reductases and their roles in protecting against oxidative stress, in ageing and in regulating protein function
Antioxidants (Basel)
7
191
2018
Rattus norvegicus (Q923M1), Mus musculus (Q9D6Y7), Homo sapiens (Q9UJ68)
Manually annotated by BRENDA team
Liu, Y.; Chong, L.; Li, X.; Tang, P.; Liu, P.; Hou, C.; Zhang, X.; Li, R.
Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A
Exp. Ther. Med.
14
2650-2656
2017
Rattus norvegicus
Manually annotated by BRENDA team