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Information on EC 1.8.4.12 - peptide-methionine (R)-S-oxide reductase and Organism(s) Homo sapiens and UniProt Accession Q9Y3D2
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1.8.4.12 peptide-methionine (R)-S-oxide reductaseIUBMB Comments
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide . While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater . 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 1.8.4.11, peptide-methionine (S)-S-oxide reductase, are found within the same protein whereas in other species, they are separate proteins [3,5]. The reaction proceeds via a sulfenic-acid intermediate [5,10]. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well . The enzyme from some species contains selenocysteine and Zn2+.
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Word Map
- 1.8.4.12
- thioredoxins
-
selenoproteins
- selenium
-
msrbs
- neisseria
-
metso
- trx
-
sulfenic
- methionine-s-sulfoxide
- meningitidis
-
thioredoxin-dependent
-
selenoenzyme
-
lincosamides
- synthesis
- biotechnology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
hide(3 overall reactions are displayed. Show all (4)>>)
Synonyms
methionine sulfoxide reductase, msrb3, msrb1, msrb2, peptide methionine sulfoxide reductase, msra/b, msrab, cbs-1, methionine-r-sulfoxide reductase, methionine sulfoxide reductase b1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
methionine sulfoxide reductase B3
MsrB
-
-
MsrB2
MsrB3
additional information
MsrB3
MsrB3 occurs in two forms, MsrB3A and MsrB3B, owing to alternative first exon splicing
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
the active site selenocysteine SeC169 is essential for enzyme activity
-
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
catalytic mechanism and the role of cofactor recycling in vivo
-
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
catalytic mechanism involving residues at positions 95, 41, 97, 77, and 80, molecular modeling, role of selenocysteine- and cysteine residues in catalysis, overview
-
PATHWAY SOURCE
PATHWAYS
BRENDA
SYSTEMATIC NAME
IUBMB Comments
peptide-methionine:thioredoxin-disulfide S-oxidoreductase [methionine (R)-S-oxide-forming]
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide [9]. While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater [10]. 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 1.8.4.11, peptide-methionine (S)-S-oxide reductase, are found within the same protein whereas in other species, they are separate proteins [3,5]. The reaction proceeds via a sulfenic-acid intermediate [5,10]. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well [11]. The enzyme from some species contains selenocysteine and Zn2+.
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
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
MsrB is specific for the R-isomer, no activity with the S-isomer
-
-
?
peptide-L-methionine-(R)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
upon oxidative stress, the overexpression of methionine sulfoxide reductase B2 leads to the preservation of mitochondrial integrity by decreasing the intracellular reactive oxygen species build-up through its scavenging role, hence contributing to cell survival and protein maintenance
-
-
?
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
dabsyl L-methionine (R)-sulfoxide + thioredoxin
dabsyl L-methionine + thioredoxin disulfide + H2O
cytosolic human thioredoxin 1, mitochondrial rat thioredoxin 2 lacking a mitochondrial signal peptide or Escherichia coli thioredoxin
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
dabsyl-L-methionine-(R)-S-oxide + dithiothreitol
dabsyl-L-methionine + DTT disulfide + H2O
-
-
-
?
peptide-L-methionine + thioredoxin disulfide + H2O
peptide-L-methionine (R)-S-oxide + thioredoxin
the study reveals a mechanism to shuttle oxidizing equivalents from the primary MsrB3 active site toward the enzyme surface, where they would be available for further dithiol-disulfide exchange reactions
-
-
?
protein L-methionine (R)-sulfoxide + thioredoxin
protein L-methionine + thioredoxin disulfide
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine (R)-sulfoxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-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
-
-
?
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form, recombinant human calmodulin, recombinant human enzyme, artificial system, determination of oxidized methionine residues being reduced by the enzyme, overview
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
-
FMsr is specific for the R-isomer
-
-
?
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
rTrx2 physically interacts with oxidized MsrB2 through a disulfide bond. Thioredoxin- and dithiothreitol-dependent activities are approximately equal
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
Msr is specific for the R-isomer
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form, enzyme variants with specificities for either free or protein-bound methionine
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is involved in regulation of protein function and in elimination of reactive oxygen species via reversible methionine formation besides protein repair in human skin
-
-
r
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction, the isozymes of MsrB are involved in lens cell viability and oxidative stress protection
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
substrates are HIV-2, which is inactivated by oxidation of its methionine residues M76 and M95, the potassium channel of the brain, the inhibitor IkappaB-alpha, or calmodulin, overview
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
the cofactor thioredoxin can be recycled in vivo by thionein due to its high content of cysteines, overview
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
isozymes MsrB1, MsrB2, and MsrB3
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction, MsrB accepts free and protein-bound substrates
-
-
r
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
-
-
?
additional information
?
-
-
downregulation of CBS-1 during replicative senescence of cells leads to accumulation of oxidized proteins and age-related increased oxidative damage
-
-
?
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, Msr 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
-
-
?
additional information
?
-
-
the enzyme protects cells against oxidative damage and plays a role in age-related and neurological diseases, like Parkinsons or Alzheimers disease
-
-
?
additional information
?
-
-
enzyme reduces oxidized methionine residues of the alpha-1-proteinase inhibitor, calmodulin, and thrombomodulin, which become reversibly inactivated upon oxidation
-
-
?
additional information
?
-
-
roles of methionine sulfoxide reductases in antioxidant defense, protein regulation via alternating it between active and inactive form, and survival, MsrB 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
?
-
-
the enzyme utilizes free and protein-bound methionine-(R)-S-oxide as substrate, but prefers the latter, methionine oxidation inactivates the proteins showing equal distribution of S-MetO and R-MetO
-
-
?
additional information
?
-
-
the thioredoxin dependence is different for selenocysteine- and cysteine-containing enzyme, overview
-
-
?
additional information
?
-
Sp1 transcription factor may play a central role in expression of the human MsrB1 gene. The MsrB1 promoter activity appears to be controlled by epigenetic modifications such as methylation
-
-
?
additional information
?
-
-
Sp1 transcription factor may play a central role in expression of the human MsrB1 gene. The MsrB1 promoter activity appears to be controlled by epigenetic modifications such as methylation
-
-
?
additional information
?
-
MsrB3 physically interacts with the sulfenic acid intermediate of these oxidized enzymes to directly form an intermolecular disulfide bond
-
-
?
additional information
?
-
-
methionine-oxidized amyloid fibrils (methionine-oxidized monomer and fibrillar apoC-II) are poor substrates for human methionine sulfoxide reductase B2. At Msr concentrations of more than 0.0005 mM, approximately 90% of monomeric MetO-apoCII is reduced. In contrast, at 0.0005 mM Msr, only 35% of fibrillar MetO-apoC-II is reduced, which increased to only 37% after incubation with a 4fold higher enzyme concentration
-
-
?
additional information
?
-
stereospecificity towards R-methionine sulfoxide
-
-
-
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
peptide-L-methionine-(R)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
upon oxidative stress, the overexpression of methionine sulfoxide reductase B2 leads to the preservation of mitochondrial integrity by decreasing the intracellular reactive oxygen species build-up through its scavenging role, hence contributing to cell survival and protein maintenance
-
-
?
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-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
-
-
?
protein L-methionine (R)-sulfoxide + thioredoxin
protein L-methionine + thioredoxin disulfide
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine (R)-sulfoxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
Msr is specific for the R-isomer
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form, enzyme variants with specificities for either free or protein-bound methionine
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is involved in regulation of protein function and in elimination of reactive oxygen species via reversible methionine formation besides protein repair in human skin
-
-
r
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
stereospecific reduction, the isozymes of MsrB are involved in lens cell viability and oxidative stress protection
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
substrates are HIV-2, which is inactivated by oxidation of its methionine residues M76 and M95, the potassium channel of the brain, the inhibitor IkappaB-alpha, or calmodulin, overview
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
the cofactor thioredoxin can be recycled in vivo by thionein due to its high content of cysteines, overview
-
-
?
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
-
-
?
additional information
?
-
-
downregulation of CBS-1 during replicative senescence of cells leads to accumulation of oxidized proteins and age-related increased oxidative damage
-
-
?
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, Msr 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
-
-
?
additional information
?
-
-
the enzyme protects cells against oxidative damage and plays a role in age-related and neurological diseases, like Parkinsons or Alzheimers disease
-
-
?
additional information
?
-
-
roles of methionine sulfoxide reductases in antioxidant defense, protein regulation via alternating it between active and inactive form, and survival, MsrB 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
?
-
Sp1 transcription factor may play a central role in expression of the human MsrB1 gene. The MsrB1 promoter activity appears to be controlled by epigenetic modifications such as methylation
-
-
?
additional information
?
-
-
Sp1 transcription factor may play a central role in expression of the human MsrB1 gene. The MsrB1 promoter activity appears to be controlled by epigenetic modifications such as methylation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
-
can act as cofactor only in vitro showing a much higher activity than thioredoxin
thioredoxin
-
-
thioredoxin
-
natural cofactor, the cofactor can be recycled in vivo by reduction via zinc-containing metallothionein, Zn-MT, after removal of the zinc ion due to its high content of cysteines, mechanism, overview
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
selenium
additional information
selenium
the presence of the selenium atom in its active site is critical for the catalytic function of this enzyme
additional information
-
native isozyme MsrB1 contains selenocysteine, while native isozymes MsrB2 and MsrB3 contain cysteine residues, the thioredoxin dependence is different for selenocysteine- and cysteine-containing enzyme, overview
additional information
-
the major isozyme of MsrB, MsrB1, is a selenoprotein, selenium affects the expression of MsrB
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
oxidative stress, e.g. caused by H2O2 up to 0.4 mM, induces enzyme expresssion
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.8
L-methionine-(R)-S-oxide
-
recombinant wild-type isozyme MsrB3 expressed in Escherichia coli
additional information
additional information
-
thioredoxin- and DTT-dependent kinetics of wild-type and mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.83
L-methionine-(R)-S-oxide
-
recombinant wild-type isozyme MsrB3 expressed in Escherichia coli
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.023
-
purified recombinant wild-type isozyme MsrB3 expressed in Escherichia coli, substrates are L-methionine-(R)-S-oxide and thioredoxin
0.173
substrate: mitochondrial rat thioredoxin 2 lacking a mitochondrial signal peptid
0.452
-
purified recombinant wild-type isozyme MsrB3 expressed in Escherichia coli, substrates are L-methionine-(R)-S-oxide and DTT
additional information
additional information
-
thioredoxin- and DTT-dependent activities of mutant enzymes, 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
chronic sun-exposure would result in a decreased expression of two main components of the methionine sulfoxide reductase system, MsrA and MsrB2
MsrB2 is downregulated during replicative senescence of WI-38 human fibroblasts
MsrB1 is highly expressed in HCC tissues and its expression correlates with the prognoses of patients with HCC after hepatectomy
-
epithelia and fibers, isozymes MsrB1 or selenoprotein R, MsrB2 or CBS-1, and MsrB3, differential expression patterns of isozymes, overview
additional information
control and stably overexpressing MsrA (from rat) and MsrB2 (from human). Zinc treatment has a pro-antioxidant effect in MOLT-4 cells by positively modulating the activity of the Msr enzymes. Overexpression of the Msr enzymes, due to their antioxidant properties, counteracts the pro-oxidant effects of zinc treatment, which lead to a cellular protection against protein oxidative damage and cell death, by reducing the production of reactive oxygen species
overexpression of human methionine sulfoxide reductase B2 in mitochondria of acute T-lymphoblastic leukemia MOLT-4 cell line, in which methionine sulfoxide reductase A is missing
expression/activities of MSRA and MSRB are significantly decreased in the epidermis of patients with vitiligo compared to healthy controls
-
cell line WI-38, young and old cells, enzyme expression pattern during cell development, senescent cells show decreased enzyme expression and activity
-
embryonic fibroblast, activity during development: downregulation during replicative senescence
-
fibroblast, young and old cells, enzyme expression pattern during cell development
additional information
-
enzyme expression level and methionine sulfoxide content in fibroblasts during development, overview
additional information
-
tissue distribution, main expression of CBS1 in muscle tissues, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular targeting is determined by alternative splicing
-
MsrB3A contains an endoplasmic reticulum signal peptide at the N-terminus and an endoplasmic reticulum retention signal at the C-terminus, and is targeted to the endoplasmic reticulum
two splice variants of the enzyme (Msr B3) that differ in their N-terminal signal sequence, which directs the protein to either the endoplasmic reticulum (ER) or mitochondria
MsrB3B contains a different signal peptide at the N-terminus and is targeted to mitochondria
two splice variants of the enzyme (Msr B3) that differ in their N-terminal signal sequence, which directs the protein to either the endoplasmic reticulum (ER) or mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
the enzyme (MsrB1) may be a therapeutic target with respect to the treatment of hepatocellular carcinoma
malfunction
physiological function
malfunction
-
knockdown of MsrB3A in mammalian cells leads to a significant decrease in the resistance to thapsigargin-induced endoplasmic reticulum (ER) stress, but had no effects on the resistance to either dithiothreitol- or tunicamycin-induced ER stress
malfunction
MsrB1 knockdown effectively inhibits tumor growth. MsrB1 knockdown reduces hepatocellular carcinoma cell migration and invasion in a transwell assay through inhibition of cytoskeletal rearrangement and spread
physiological function
-
MSRB2 plays an important function in protecting cones from multiple type of oxidative stress and is critical in preserving central vision
physiological function
-
methionine sulfoxide reductase B3 protects from endoplasmic reticulum (ER) stress. Drosophila flies overexpressing human MsrB3A exhibit significantly increased resistance to ER stress induced by dithiothreitol (cell viability is enhanced by 40% and 30% in the treatment of 0.5 and 1 mM dithiothreitol, respectively). These flies also show slightly enhanced resistance to tunicamycin-induced ER stress. The enzyme may be involved in the regulation of ER homeostasis. Overexpression of MsrB3A in mammalian cells increases resistance to dithiothreitol- and thapsigargin-induced endoplasmic reticulum (ER) stresses. However, MsrB3A overexpression has no effect on the resistance to tunicamycin-induced ER stress
physiological function
-
neuronal expression of isoform MsrB3A renders Drosophilaflies resistant to oxidative stress. These flies also show significantly enhanced cold (4°C) and heat (37°C) tolerance. Expression of isoform MsrB3A in the whole body and nervous system extends the lifespan of fruit flies at 29°C by 43-50% and 12-37%, respectively. Additionally, isoform MsrB3A overexpression significantly delays the age-related decline in locomotor activity and fecundity
physiological function
methionine sulfoxide reductase B1 regulates hepatocellular carcinoma cell proliferation and invasion via the mitogen-activated protein kinase pathway and epithelial-mesenchymal transition
physiological function
MsrB is implicated in human lens epithelial cell viability
physiological function
the enzyme (MsrB3) is able to function in vivo to complement a bacterial strain deficient in endogenous Msr
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). MSRB2_HUMAN
182
0
19536
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, crystals diffracting to 1.87 A resolution, the MsrB3 structure is determined by using X-ray crystallography
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C105S
-
site-directed mutagenesis, unaltered activity compared to the wild-type enzyme
C169S
-
site-directed mutagenesis, active site mutant, completely inactive mutant
H77G
-
site-directed mutagenesis, mutation of isozyme MsrB3 leads to highly reduced activity with cofactor thioredoxin or DTT compared to wild-type MsrB3
H77G/I81E/N97F
-
site-directed mutagenesis, mutation of isozyme MsrB3, inactive mutant
H77G/N97F
-
site-directed mutagenesis, mutation of isozyme MsrB3, inactive mutant
I81E
-
site-directed mutagenesis, mutation of isozyme MsrB3 leads to slightly increased activity with cofactor thioredoxin and reduced activcity with DTT compared to wild-type MsrB3
N97F
-
site-directed mutagenesis, mutation of isozyme MsrB3, the mutant is inactive with cofactor thioredoxin and shows highly reduced activity with cofactor DTT compared to wild-type MsrB3
N97Y
-
site-directed mutagenesis, mutation of isozyme MsrB3, the mutant shows highly reduced activity with cofactor DTT or thioredoxin compared to wild-type MsrB3
W110A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
additional information
-
substitution of Cys residues abolish the enzyme's activity with thioredoxin and increase the DTT-dependent activity, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography
-
recombinant wild-type and mutant isozyme MsrB3 from Escherichia coli strain BL21(DE3)
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
human MOLT-4 cell line are stably transfected with the pLXSN retroviral expression vector based on the Moloney murine leukemia virus and Moloney murine sarcoma virus to generate a replication-deficient recombinant retrovirus containing the rat MsrA and the human MsrB2 cDNA. The oxidized protein repair enzymes MsrA and MsrB2, when overexpressed in the cells, are able to counteract the zinc-mediated damaging effects
expressed in Drosophila melanogaster, in A-549 cells and human dermal fibroblasts
-
expression in Escherichia coli as a fusion protein with GST which is subsequently cleaved after purification
expression in in Escherichia coli as a fusion with maltose binding protein
expression of wild-type and mutant isozyme MsrB3 in Escherichia coli strain BL21(DE3)
-
overexpression of truncated wild-type and mutant enzymes as His-tagged proteins in Escherichia coli, functional coexpression of CBS1 in oocytes with Drosophila melanogaster ShC/B potassium channel
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moskovitz, J.; Poston, J.M.; Berlett, B.S.; Nosworthy, N.J.; Szczepanowski, R.; Stadtman, E.R.
Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity
J. Biol. Chem.
275
14167-14172
2000
Homo sapiens
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, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Homo sapiens, Mus musculus, Neisseria gonorrhoeae, Neisseria meningitidis, Saccharomyces cerevisiae, Streptococcus gordonii, Streptococcus gordonii (Q9LAM9), 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
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
Jung, S.; Hansel, A.; Kasperczyk, H.; Hoshi, T.; Heinemann, S.H.
Activity, tissue distribution and site-directed mutagenesis of a human peptide methionine sulfoxide reductase of type B: hCBS1
FEBS Lett.
527
91-94
2002
Homo sapiens
Picot, C.R.; Perichon, M.; Cintrat, J.C.; Friguet, B.; Petropoulos, I.
The peptide methionine sulfoxide reductases, MsrA and MsrB (hCBS-1), are downregulated during replicative senescence of human WI-38 fibroblasts
FEBS Lett.
558
74-78
2004
Homo sapiens
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
Homo sapiens
Lowther, W.T.; Weissbach, H.; Etienne, F.; Brot, N.; Matthews, B.W.
The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB
Nat. Struct. Biol.
9
348-352
2002
Escherichia coli (P0A746), Neisseria gonorrhoeae (P14930), Neisseria gonorrhoeae, Homo sapiens (Q9Y3D2)
Schallreuter, K.U.; Rubsam, K.; Chavan, B.; Zothner, C.; Gillbro, J.M.; Spencer, J.D.; Wood, J.M.
Functioning methionine sulfoxide reductases A and B are present in human epidermal melanocytes in the cytosol and in the nucleus
Biochem. Biophys. Res. Commun.
342
145-152
2006
Homo sapiens
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, Homo sapiens, Mus musculus
Marchetti Maria, A.; Pizarro Gresin, O.; Sagher, D.; Deamicis, C.; Brot, N.; Hejtmancik, J.F.; Weissbach, H.; Kantorow, M.
Methionine sulfoxide reductases B1, B2, and B3 are present in the human lens and confer oxidative stress resistance to lens cells
Invest. Ophthalmol. Vis. Sci.
46
2107-2112
2005
Homo sapiens
Kim, H.Y.; Gladyshev, V.N.
Different catalytic mechanisms in mammalian selenocysteine- and cysteine-containing methionine-R-sulfoxide reductases
PLoS Biol.
3
2080-2089
2005
Homo sapiens, Mus musculus
-
Sagher, D.; Brunell, D.; Hejtmancik, J.F.; Kantorow, M.; Brot, N.; Weissbach, H.
Thionein can serve as a reducing agent for the methionine sulfoxide reductases
Proc. Natl. Acad. Sci. USA
103
8656-8661
2006
Escherichia coli, Homo sapiens
Cabreiro, F.; Picot, C.R.; Perichon, M.; Friguet, B.; Petropoulos, I.
Overexpression of methionine sulfoxide reductases A and B2 protects MOLT-4 cells against zinc-induced oxidative stress
Antioxid. Redox Signal.
11
215-225
2009
Homo sapiens (Q9Y3D2)
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 (Q78J03), Homo sapiens (Q8IXL7)
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
Drosophila melanogaster, Neisseria meningitidis, Bacillus subtilis (P54155), Mus musculus (Q8BU85), Homo sapiens (Q8IXL7)
De Luca, A.; Sacchetta, P.; Nieddu, M.; Di Ilio, C.; Favaloro, B.
Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxide reductase B1 (MsrB1) promoter
BMC Mol. Biol.
8
39
2007
Homo sapiens (Q9NZV6), Homo sapiens
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
Homo sapiens (Q8IXL7), Homo sapiens (Q9Y3D2), Homo sapiens
Cabreiro, F.; Picot, C.R.; Perichon, M.; Castel, J.; Friguet, B.; Petropoulos, I.
Overexpression of mitochondrial methionine sulfoxide reductase B2 protects leukemia cells from oxidative stress-induced cell death and protein damage
J. Biol. Chem.
283
16673-16681
2008
Homo sapiens (Q9Y3D2)
Schallreuter, K.U.; Ruebsam, K.; Gibbons, N.C.; Maitland, D.J.; Chavan, B.; Zothner, C.; Rokos, H.; Wood, J.M.
Methionine sulfoxide reductases A and B are deactivated by hydrogen peroxide (H2O2) in the epidermis of patients with vitiligo
J. Invest. Dermatol.
128
808-815
2008
Homo sapiens (Q9NZV6), Homo sapiens
Binger, K.J.; Griffin, M.D.; Heinemann, S.H.; Howlett, G.J.
Methionine-oxidized amyloid fibrils are poor substrates for human methionine sulfoxide reductases A and B2
Biochemistry
49
2981-2983
2010
Homo sapiens
Pascual, I.; Larrayoz, I.M.; Campos, M.M.; Rodriguez, I.R.
Methionine sulfoxide reductase B2 is highly expressed in the retina and protects retinal pigmented epithelium cells from oxidative damage
Exp. Eye Res.
90
420-428
2010
Homo sapiens, Macaca mulatta
Lim, D.H.; Han, J.Y.; Kim, J.R.; Lee, Y.S.; Kim, H.Y.
Methionine sulfoxide reductase B in the endoplasmic reticulum is critical for stress resistance and aging in Drosophila
Biochem. Biophys. Res. Commun.
419
20-26
2012
Homo sapiens
Kwak, G.H.; Lim, D.H.; Han, J.Y.; Lee, Y.S.; Kim, H.Y.
Methionine sulfoxide reductase B3 protects from endoplasmic reticulum stress in Drosophila and in mammalian cells
Biochem. Biophys. Res. Commun.
420
130-135
2012
Homo sapiens
Javitt, G.; Cao, Z.; Resnick, E.; Gabizon, R.; Bulleid, N.J.; Fass, D.
Structure and electron-transfer pathway of the human methionine sulfoxide reductase MsrB3
Antioxid. Redox Signal.
33
665-678
2020
Homo sapiens (Q8IXL7), 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
Homo sapiens (Q8IXL7), Homo sapiens (Q9NZV6)
Cao, Z.; Mitchell, L.; Hsia, O.; Scarpa, M.; Caldwell, S.T.; Alfred, A.D.; Gennaris, A.; Collet, J.F.; Hartley, R.C.; Bulleid, N.J.
Methionine sulfoxide reductase B3 requires resolving cysteine residues for full activity and can act as a stereospecific methionine oxidase
Biochem. J.
475
827-838
2018
Homo sapiens (Q8IXL7)
He, Q.; Li, H.; Meng, F.; Sun, X.; Feng, X.; Chen, J.; Li, L.; Liu, J.
Methionine sulfoxide reductase B1 regulates hepatocellular carcinoma cell proliferation and invasion via the mitogen-activated protein kinase pathway and epithelial-mesenchymal transition
Oxid. Med. Cell. Longev.
2018
5287971
2018
Homo sapiens (Q9NZV6), Homo sapiens
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