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Information on EC 1.8.4.11 - peptide-methionine (S)-S-oxide reductase and Organism(s) Mus musculus and UniProt Accession Q9D6Y7
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1.8.4.11 peptide-methionine (S)-S-oxide reductaseIUBMB 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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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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, protein-methionine-s-oxide reductase, peptide methionine sulfoxide reductase a, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
methionine sulfoxide reductase A
-
MsrA
-
methionine S-oxide reductase (S-form oxidizing)
-
-
-
-
MsrA
-
-
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)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
-
-
-
?
dabsyl-L-methionine-(S)-S-oxide + dithiothreitol
dabsyl-L-methionine + DTT disulfide + H2O
-
-
-
?
L-methionine (S)-sulfoxide + 2 dithiothreitol
L-methionine + dithiothreitol disulfide + H2O
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
r
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
stereospecific reduction
-
-
?
protein-L-methionine (S)-S-oxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
Met sulfoxide residues in Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
alpha-synuclein + thioredoxin disulfide + H2O
?
-
Met1 and Met5 within alpha-synuclein are oxidized to (S)-methionine sulfoxide
-
-
?
alpha1-antitrypsin + thioredoxin disulfide + H2O
?
-
Met358 within alpha1-antitrypsin is oxidized to (S)-methionine sulfoxide
-
-
?
apolipoprotein A-I + dithiothreitol
?
-
the myristoylated enzyme reduces the methionine sulfoxides in apolipoprotein A-I four times faster than nonmyristoylated enzyme
-
-
?
calmodulin + thioredoxin disulfide + H2O
?
-
Met77 within calmodulin is oxidized to (S)-methionine sulfoxide
-
-
r
dabsyl-L-methionine-(S)-S-oxide + DTT
dabsyl-L-methionine + DTT disulfide + H2O
-
stereospecific reduction
-
-
?
dabsyl-L-methionine-(S)-S-oxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
L-methionine (S)-sulfoxide + dithiothreitol
?
-
the myristoylated enzyme form reduces methionine sulfoxide in protein much faster than the nonmyristoylated form
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
L-methionine (S)-sulfoxide + 2 dithiothreitol
L-methionine + dithiothreitol disulfide + H2O
-
-
-
?
L-methionine (S)-sulfoxide + 2 dithiothreitol
L-methionine + dithiothreitol disulfide + H2O
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrA is specific for the S-form
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrA is specific for the S-form, there exist enzyme variants with specificities for either free or protein-bound methionine
-
-
?
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction, free methionine-(S)-S-oxide
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
MsrA is involved in repair of oxidized proteins
-
-
?
additional information
?
-
the lack of the MsrA gene in conjunction with prolonged selenium deficient diet causes decreased antioxidant capability and enhanced protein oxidation
-
-
?
additional information
?
-
MsrA repairs methionine oxidized alpha-crystallin and restores the chaperone activity of alpha-crystallin lost upon methionine oxidation, Met-68 of alphabeta-crystallin is oxidized to protein methionine sulfoxide in the actual lens
-
-
?
additional information
?
-
-
recycling of free methionine, enzyme reverses the oxidative damage at methionine protein residues oxidized to methionine sulfoxide being a major cause of aging and age-related diseases, MsrA can regulate protein function, be involved in signal transduction, and prevent accumulation of faulty proteins, MsrB has several different physiological repair and regulatory functions, overview, oxidation of 2 essential methionine residues of HIV-2 particles can inactivate the virus and prevent infection of human cells
-
-
?
additional information
?
-
-
the enzyme protect cells against oxidative damage and plays a role in age-related diseases
-
-
?
additional information
?
-
-
MsrA is a regulator of antioxidant defense and lifespan in mammals
-
-
?
additional information
?
-
-
roles of methionine sulfoxide reductases in antioxidant defense, protein regulation via alternating it between active and inactive form, and survival, MsrA protects cells from the cytotoxic effects of reactive oxygen species, ROS, overview, the enzyme is involved in age-related diseases such as Alzheimer's or Parkinson's diseases as well as in diseases caused by prions, mechanism, overview, enzyme involvement in protein repair and associated factors, protein regulation pathway, overview
-
-
?
additional information
?
-
-
role of subcellular localization in structure-function relationship of the isozymes, overview
-
-
?
additional information
?
-
-
MsrA knockout mice have a shorter life span, are more sensitive to hyperbaric oxygen and had a neurological defect that resuls in abnormal walking
-
-
?
additional information
?
-
-
MsrA null mutant mice exhibit a shortened lifespan and present higher levels of protein carbonyls when exposed to hyperoxia, which indicates an increased sensitivity towards oxidative stress
-
-
?
additional information
?
-
-
no oxidation or reduction of L-methionine in 14-3-3 zeta/delta protein, actin, alpha-crystallin A, alpha-crystallin B, apolipoprotein A, glutamine synthetase, peroxiredoxin 6, and thioredoxin
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
protein-L-methionine (S)-S-oxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
Met sulfoxide residues in Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
L-methionine (S)-sulfoxide + dithiothreitol
?
-
the myristoylated enzyme form reduces methionine sulfoxide in protein much faster than the nonmyristoylated form
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrA is specific for the S-form
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrA is specific for the S-form, there exist enzyme variants with specificities for either free or protein-bound methionine
-
-
?
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
-
MsrA is involved in repair of oxidized proteins
-
-
?
additional information
?
-
the lack of the MsrA gene in conjunction with prolonged selenium deficient diet causes decreased antioxidant capability and enhanced protein oxidation
-
-
?
additional information
?
-
-
recycling of free methionine, enzyme reverses the oxidative damage at methionine protein residues oxidized to methionine sulfoxide being a major cause of aging and age-related diseases, MsrA can regulate protein function, be involved in signal transduction, and prevent accumulation of faulty proteins, MsrB has several different physiological repair and regulatory functions, overview, oxidation of 2 essential methionine residues of HIV-2 particles can inactivate the virus and prevent infection of human cells
-
-
?
additional information
?
-
-
the enzyme protect cells against oxidative damage and plays a role in age-related diseases
-
-
?
additional information
?
-
-
MsrA is a regulator of antioxidant defense and lifespan in mammals
-
-
?
additional information
?
-
-
roles of methionine sulfoxide reductases in antioxidant defense, protein regulation via alternating it between active and inactive form, and survival, MsrA protects cells from the cytotoxic effects of reactive oxygen species, ROS, overview, the enzyme is involved in age-related diseases such as Alzheimer's or Parkinson's diseases as well as in diseases caused by prions, mechanism, overview, enzyme involvement in protein repair and associated factors, protein regulation pathway, overview
-
-
?
additional information
?
-
-
MsrA knockout mice have a shorter life span, are more sensitive to hyperbaric oxygen and had a neurological defect that resuls in abnormal walking
-
-
?
additional information
?
-
-
MsrA null mutant mice exhibit a shortened lifespan and present higher levels of protein carbonyls when exposed to hyperoxia, which indicates an increased sensitivity towards oxidative stress
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
thioredoxin
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
H2O2
in the mouse enzyme, the sulfenic acid formed at the catalytic Cys residue is vulnerable to irreversible oxidation to cysteine sulfinic acid resulting in inactivation. Hyperoxidation is controlled by the presence or absence of residue Met229 in the carboxyl terminal domain. Mouse msrA becomes insensitive to hyperoxidation when the Met229 is mutated. Hyperoxidation occurs so long as the methionine is located within the 14 carboxyl terminal residues. Met229 may form a stable, non-covalent bond with Trp74 at the active site, preventing formation of a protective sulfenylamide with Cys72 sulfenic acid
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.197
Calmodulin
-
myristoylated enzyme, in 20 mM Tris-HCl, pH 7.5, 1 mM CaCl2, at 37°C
0.34
dabsyl-L-methionine-(S)-S-oxide
-
recombinant wild-type MsrA, with DTT, pH 7.5, 37°C
4.3
dabsyl-L-methionine-(S)-S-oxide
-
recombinant truncated MsrA DELTA(1-46), with DTT, pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.28
dabsyl-L-methionine-(S)-S-oxide
-
recombinant wild-type MsrA, with DTT, pH 7.5, 37°C
0.78
dabsyl-L-methionine-(S)-S-oxide
-
recombinant truncated MsrA DELTA(1-46), with DTT, pH 7.5, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.099
-
purified recombinant truncated MsrA DELTA(1-46), substrates DTT and dabsyl-L-methionine-(S)-S-oxide
0.238
-
purified recombinant wild-type MsrA, substrates DTT and dabsyl-L-methionine-(S)-S-oxide
additional information
-
activities in wild-type and mutant mice in different organs during 2 days, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
a knockout mouse strain of the methionine sulfoxide reductase A gene (MsrA-/-) causes an enhanced neurodegeneration in brain hippocampus relative to its wild-type control mouse brain. Deficiency in MsrA activity fosters oxidative-stress that is manifested by the accumulation of faulty proteins (via methionine oxidation), deposition of aggregated proteins, and premature brain cell death
MsrA-/- mice have compromised complex task learning capabilities relative to wild-type mice. MsrA-/- mice exhibit lower locomotor activity and altered gait that exacerbate with age. MsrA-/- mice are less responsive to amphetamine treatment. Relative to wild-type mice, MsrA-/- brains contain significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine are observed at 16 months of age. Striatal regions of MsrA-/- mice show an increase of dopamine release parallel to observed dopamine levels. It is suggested that dopamine regulation and signaling pathways are impaired in MsrA-/- mice, which may contribute to their abnormal behavior
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
maximal expression level of MsrA in kidney and liver, followed by heart, lung, brain, skeletal muscle, retina, testis, bone marrow, and blood
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
subcellular localization is regulated by alternative splicing, overview
-
additional information
-
post-translationally occuring subcellular targeting and distribution of isozymes, overview, several forms are generated from a single translation form
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
enzyme-deficient mice are more susceptible to kidney ischemia/reperfusion injury than wild type mice. Deletion of the enzyme enhances renal functional and morphological impairments, congestion, inflammatory responses, and oxidative stress under ischemia/reperfusion conditions
metabolism
physiological function
malfunction
MsrA deficiency increases both basal and acetaminophen-induced thioredoxin reductase 1 expression levels, likely through increased Nrf2 activation. Conversely, MsrA overexpression diminishes the augmented thioredoxin reductase 1 levels in acetaminophen-treated MsrA(-/-) hepatocytes, reducing susceptibility against acetaminophen-induced cytotoxicity
malfunction
MsrA-/- mice are more susceptible to lipopolysaccharide (LPS) induced lethal shock than wild-type (MsrA+/+) mice. Serum levels of the proinflammatory cytokines IL-6 and TNF-alpha induced by LPS are higher in MsrA-/- than in MsrA+/+ mice. MsrA deficiency in the bone marrow-derived macrophages (BMDMs) also increases the LPS-induced cytotoxicity as well as TNF-alpha level. Basal and LPS-induced reactive oxygen species (ROS) levels are higher in MsrA-/- than in MsrA+/+ bone marrow-derived macrophages. Phosphorylation levels of p38, JNK, and ERK are higher in MsrA-/- than in MsrA+/+ BMDMs in response to LPS, suggesting that MsrA deficiency increases MAPK activation. MsrA deficiency increased the expression and nuclear translocation of NF-kappaB and the expression of inducible nitric oxide synthase, a target gene of NF-kappaB, in response to lipopolysaccharide (LPS)
physiological function
MsrA knockout mice exhibit altered locomotor activity and brain dopamine levels as function of age, caloric restriction has a neutralization effect on MsrA ablation
physiological function
overexpression of MsrA does not protect MEF cells from oxidative stress
physiological function
construction of an ER-targeted MsrA construct. The overexpression of ER-targeted MsrA significantly increases cellular resistance to H2O2-induced oxidative stress and significantly enhances resistance to dithiothreitol-induced ER stress. The construct has no positive effects on the resistance to ER stresses induced by tunicamycin and thapsigargin
physiological function
MsrA gene-deleted (MsrA-/-) hepatocytes show higher susceptibility to acetaminophen-induced cytotoxicity than wild-type cells. MsrA deficiency increases acetaminophen-induced glutathione depletion and reactive oxygen species production. Acetaminophen-treatment increases Nrf2 activation more profoundly in MsrA-/- than in wild-type hepatocytes, and basal thioredoxin reductase 1 levels are significantly higher in MsrA-/- than in wild-type hepatocytes
physiological function
it is proposed that MsrA-dependent 14-3-3 zeta ubiquitination affects the regulation of alpha synuclein degradation and dopamine synthesis in the brain
physiological function
the antioxidant enzyme methionine sulfoxide reductase A (MsrA) interacts with Jab1/CSN5 and regulates its function. The interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival
physiological function
the enzyme (MsrA) protects against LPS-induced septic shock, and negatively regulates proinflammatory responses via inhibition of the ROS-MAPK-NF-kappaB signaling pathways
physiological function
the enzyme protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression
metabolism
-
methionine sulfoxide reductase A is an essential enzyme in the antioxidant system which scavenges reactive oxygen species through cyclic oxidation and reduction of methionine and methionine sulfoxide
metabolism
-
the enzyme participates in regulating methionine metabolism and the trans-sulfuration pathway under normal and ischemia/reperfusion conditions
physiological function
-
methionine sulfoxide reductase A repairs oxidized methionine residues within proteins and may also function as a general antioxidant, lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span, MsrA knockout mice are more susceptible to oxidative stress induced by paraquat, there is no difference between MsrA knockout and control mice in either their median or maximum life span
physiological function
-
the enzyme protects the kidney against ischemia/reperfusion injury. This protection is associated with reduced oxidative stress and inflammatory responses. The enzyme regulates H2S production during ischemia/reperfusion by modulating the expression and activity of the cystathionine-beta-synthase and cystathionine-gamma-lyase enzymes
physiological function
-
mouse model of Alzheimer's disease, a mouse that overexpresses amyloid precursor protein and Abeta in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins. MsrA-deficient mice expressing amyloid precursor protein exhibit higher levels of soluble Abeta in brain. Mitochondrial respiration and the activity of cytochrome c oxidase are compromised in the MsrA-deficient mice expressing amyloid precursor protein compared with control mice
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MSRA_MOUSE
233
0
25988
Swiss-Prot
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
16000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
M229V
mutation to corresponding residue of human enzyme, which is not hyperoxidized by H2O2. Mutant is insensitive to hyperoxidation
additional information
additional information
-
construction of a MsrA null mutant which exhibits a neurological disorder in the form of ataxia, is more sensitive to oxidative stress, and has by about 40% shorter life span than the wild-type mice at normal oxygen conditions and 10% at hyperoxic conditions
additional information
-
knockout mutants show shortened life span and have neurological lesions
additional information
-
generation of MsrA-deficient mutant mice, the mutant mice show tip-toe-walking, reduced lifespan under hyperoxic conditions and increased sensitivity to oxidative stress compared to wild-type mice, phenotype overview
additional information
-
msrA gene disruption leads to a shortened life span both under normoxic and hyperoxic conditions, MsrA null mutant mice shows greater sensitivity to hyperoxic conditions compared to wild-type mice, construction of MsrA overexpressing strains, phenotypes, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genomic structure, alternative splicing variants, overview, expression of GFP-tagged and/or His-tagged mitochondrial and cytosolic MsrAs in CV-1 cells
msrA, DNA and amino acid sequence determination and analysis, expression of C-terminally His-tagged or GFP-tagged wild-type or truncated MsrA in Escherichia coli strain BL21(DE3), expression of MsrA isozymes in Saccharomyces cerevisiae, subcellular localization of the recombinant enzymes in cytosol and mitochondria, overview
-
overexpression of MsrA leads to increased resistance to reactive oxygen species
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
mouse model of Alzheimer's disease, a mouse that overexpresses amyloid precursor protein and Abeta in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins. MsrA-deficient mice expressing amyloid precursor protein exhibit higher levels of soluble Abeta in brain. Mitochondrial respiration and the activity of cytochrome c oxidase are compromised in the MsrA-deficient mice expressing amyloid precursor protein compared with control mice
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moskovitz, J.; Bar-Noy, S.; Williams, W.M.; Requena, J.; Berlett, B.S.; Stadtman, E.R.
Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals
Proc. Natl. Acad. Sci. USA
98
12920-12925
2001
Mus musculus
Weissbach, H.; Resnick, L.; Brot, N.
Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage
Biochim. Biophys. Acta
1703
203-212
2005
Bos taurus, Dickeya chrysanthemi, Drosophila melanogaster, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Homo sapiens, Mus musculus, Neisseria gonorrhoeae, Neisseria meningitidis, Saccharomyces cerevisiae, Streptococcus gordonii, Streptococcus pneumoniae
Moskovitz, J.
Methionine sulfoxide reductases: ubiquitous enzymes involved in antioxidant defense, protein regulation, and prevention of aging-associated diseases
Biochim. Biophys. Acta
1703
213-219
2005
Arabidopsis thaliana, Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Staphylococcus aureus, Mus musculus, Sus scrofa
Kim, H.Y.; Gladyshev, V.N.
Role of structural and functional elements of mouse methionine-S-sulfoxide reductase in its subcellular distribution
Biochemistry
44
8059-8067
2005
Mus musculus
Kim, H.Y.; Gladyshev, V.N.
Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases
BMC Mol. Biol.
7
11
2006
Homo sapiens, Homo sapiens (Q9UJ68), Drosophila melanogaster (P08761), Mus musculus (Q9D6Y7)
Moskovitz, J.
Roles of methionine suldfoxide reductases in antioxidant defense, protein regulation and survival
Curr. Pharm. Des.
11
1451-1457
2005
Arabidopsis thaliana, Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Staphylococcus aureus, Mus musculus, Sus scrofa
Kim, H.Y.; Kim, J.R.
Thioredoxin as a reducing agent for mammalian methionine sulfoxide reductases B lacking resolving cysteine
Biochem. Biophys. Res. Commun.
371
490-494
2008
Mus musculus (Q9D6Y7)
Kim, H.Y.; Gladyshev, V.N.
Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammals
Biochem. J.
407
321-329
2007
Bos taurus, Escherichia coli, Homo sapiens, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Neisseria meningitidis, Populus trichocarpa, Mus musculus (Q9D6Y7)
Le, D.T.; Liang, X.; Fomenko, D.E.; Raza, A.S.; Chong, C.K.; Carlson, B.A.; Hatfield, D.L.; Gladyshev, V.N.
Analysis of methionine/selenomethionine oxidation and methionine sulfoxide reductase function using methionine-rich proteins and antibodies against their oxidized forms
Biochemistry
47
6685-6694
2008
Mus musculus (Q9D6Y7)
Pal, R.; Oien, D.B.; Ersen, F.Y.; Moskovitz, J.
Elevated levels of brain-pathologies associated with neurodegenerative diseases in the methionine sulfoxide reductase A knockout mouse
Exp. Brain Res.
180
765-774
2007
Mus musculus (Q9D6Y7), Mus musculus
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
Oien, D.B.; Osterhaus, G.L.; Latif, S.A.; Pinkston, J.W.; Fulks, J.; Johnson, M.; Fowler, S.C.; Moskovitz, J.
MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels
Free Radic. Biol. Med.
45
193-200
2008
Mus musculus (Q9D6Y7), Mus musculus
Moskovitz, J.
Prolonged selenium-deficient diet in MsrA knockout mice causes enhanced oxidative modification to proteins and affects the levels of antioxidant enzymes in a tissue-specific manner
Free Radic. Res.
41
162-171
2007
Mus musculus (Q9D6Y7)
Brennan, L.A.; Lee, W.; Giblin, F.J.; David, L.L.; Kantorow, M.
Methionine sulfoxide reductase A (MsrA) restores alpha-crystallin chaperone activity lost upon methionine oxidation
Biochim. Biophys. Acta
1790
1665-1672
2009
Mus musculus (Q9D6Y7), Homo sapiens (Q9UJ68)
Salmon, A.B.; Perez, V.I.; Bokov, A.; Jernigan, A.; Kim, G.; Zhao, H.; Levine, R.L.; Richardson, A.
Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span
FASEB J.
23
3601-3608
2009
Mus musculus
Oien, D.B.; Osterhaus, G.L.; Lundquist, B.L.; Fowler, S.C.; Moskovitz, J.
Caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse
Neurosci. Lett.
468
38-41
2010
Mus musculus (Q9D6Y7), Mus musculus
Zhao, H.; Kim, G.; Liu, C.; Levine, R.L.
Transgenic mice overexpressing methionine sulfoxide reductase A: characterization of embryonic fibroblasts
Free Radic. Biol. Med.
49
641-648
2010
Mus musculus (Q9D6Y7), Mus musculus
Kim, J.I.; Choi, S.H.; Jung, K.J.; Lee, E.; Kim, H.Y.; Park, K.M.
Protective role of methionine sulfoxide reductase A against ischemia/reperfusion injury in mouse kidney and its involvement in the regulation of trans-sulfuration pathway
Antioxid. Redox Signal.
18
2241-2250
2013
Mus musculus
Lim, J.C.; Kim, G.; Levine, R.L.
Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A
Free Radic. Biol. Med.
61C
257-264
2013
Mus musculus
Lim, J.C.; Gruschus, J.M.; Ghesquiere, B.; Kim, G.; Piszczek, G.; Tjandra, N.; Levine, R.L.
Characterization and solution structure of mouse myristoylated methionine sulfoxide reductase A
J. Biol. Chem.
287
25589-25595
2012
Mus musculus
Jia, P.; Zhang, C.; Jia, Y.; Webster, K.A.; Huang, X.; Kochegarov, A.A.; Lemanski, S.L.; Lemanski, L.F.
Identification of a truncated form of methionine sulfoxide reductase A expressed in mouse embryonic stem cells
J. Biomed. Sci.
18
46
2011
Mus musculus
Kim, J.Y.; Kim, Y.; Kwak, G.H.; Oh, S.Y.; Kim, H.Y.
Over-expression of methionine sulfoxide reductase A in the endoplasmic reticulum increases resistance to oxidative and ER stresses
Acta Biochim. Biophys. Sin. (Shanghai)
46
415-419
2014
Mus musculus (Q9D6Y7)
Moskovitz, J.; Du, F.; Bowman, C.F.; Yan, S.S.
Methionine sulfoxide reductase A affects beta-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease
Am. J. Physiol. Endocrinol. Metab.
310
E388-E393
2016
Mus musculus
Singh, M.P.; Kim, K.Y.; Kim, H.Y.
Methionine sulfoxide reductase A deficiency exacerbates acute liver injury induced by acetaminophen
Biochem. Biophys. Res. Commun.
484
189-194
2017
Mus musculus (Q9D6Y7)
Kim, G.; Levine, R.L.
A methionine residue promotes hyperoxidation of the catalytic cysteine of mouse methionine sulfoxide reductase A
Biochemistry
55
3586-3593
2016
Mus musculus (Q9D6Y7), Mus musculus, Homo sapiens (Q9UJ68), Homo sapiens
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)
Jiang, B.; Adams, Z.; Moonah, S.; Shi, H.; Maupin-Furlow, J.; Moskovitz, J.
The antioxidant enzyme methionine sulfoxide reductase A (MsrA) interacts with Jab1/CSN5 and regulates its function
Antioxidants (Basel)
9
452
2020
Mus musculus (Q9D6Y7)
Singh, M.P.; Kim, K.Y.; Kwak, G.H.; Baek, S.H.; Kim, H.Y.
Methionine sulfoxide reductase A protects against lipopolysaccharide-induced septic shock via negative regulation of the proinflammatory responses
Arch. Biochem. Biophys.
631
42-48
2017
Mus musculus (Q9D6Y7)
Singh, M.P.; Kwak, G.H.; Kim, K.Y.; Kim, H.Y.
Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression
Biochem. Biophys. Res. Commun.
487
695-701
2017
Mus musculus (Q9D6Y7)
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