Information on EC 1.8.4.12 - peptide-methionine (R)-S-oxide reductase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
1.8.4.12
-
RECOMMENDED NAME
GeneOntology No.
peptide-methionine (R)-S-oxide reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine + thioredoxin disulfide + H2O = L-methionine (S)-S-oxide + thioredoxin
show the reaction diagram
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
show the reaction diagram
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (S)-S-oxide + thioredoxin
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
methionine metabolism
-
-
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+.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
strain NCTC 11168
-
-
Manually annotated by BRENDA team
strain NCTC 11168
-
-
Manually annotated by BRENDA team
ECW-30R
UniProt
Manually annotated by BRENDA team
enzyme belongs to the metal-containing MsrB group I
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
; gene msr encodes an enzyme showing both MsrA, methionine S-oxide reductase (S-form oxidizing), and MsrB, methionine S-oxide reductase (R-form oxidizing), activity
-
-
Manually annotated by BRENDA team
ATCC 43049
-
-
Manually annotated by BRENDA team
strain NRC-1
-
-
Manually annotated by BRENDA team
strain NRC-1
-
-
Manually annotated by BRENDA team
strain 26695, enzyme forms MsrA and MsrB are fused together forming a single protein termed Msr
-
-
Manually annotated by BRENDA team
strain 100-23 in murine gut
-
-
Manually annotated by BRENDA team
strain 100-23 in murine gut
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
DSM 6242
-
-
Manually annotated by BRENDA team
strain C2A
-
-
Manually annotated by BRENDA team
strain Fusaro
-
-
Manually annotated by BRENDA team
strain Fusaro
-
-
Manually annotated by BRENDA team
strain Go1
-
-
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicum
strain delta H
UniProt
Manually annotated by BRENDA team
DSM 2160
-
-
Manually annotated by BRENDA team
strain MS11, variant VD300, bifunctional enzyme MsrA/B, gene pilB
-
-
Manually annotated by BRENDA team
precursor
SwissProt
Manually annotated by BRENDA team
no activity in Aeropyrum pernix K1
-
-
-
Manually annotated by BRENDA team
no activity in Aquifex aeolicus
-
-
-
Manually annotated by BRENDA team
no activity in Archaeoglobus fulgidus DSM 4304
-
-
-
Manually annotated by BRENDA team
no activity in Bifidobacterium longum
NCC2705
-
-
Manually annotated by BRENDA team
no activity in Bifidobacterium longum NCC2705
NCC2705
-
-
Manually annotated by BRENDA team
no activity in Clostridium tetani
strain E88
-
-
Manually annotated by BRENDA team
no activity in Clostridium tetani E88
strain E88
-
-
Manually annotated by BRENDA team
no activity in Ferroplasma acidarmanus
-
-
-
Manually annotated by BRENDA team
no activity in Methanocaldococcus jannaschii
DSM 2661
-
-
Manually annotated by BRENDA team
no activity in Methanococcus maripaludis
strain S2
-
-
Manually annotated by BRENDA team
no activity in Methanococcus maripaludis S2
strain S2
-
-
Manually annotated by BRENDA team
no activity in Methanopyrus kandleri
strain AV19
-
-
Manually annotated by BRENDA team
no activity in Methanopyrus kandleri AV19
strain AV19
-
-
Manually annotated by BRENDA team
no activity in Nanoarchaeum equitans
Kin4-M
-
-
Manually annotated by BRENDA team
no activity in Nanoarchaeum equitans Kin4-M
Kin4-M
-
-
Manually annotated by BRENDA team
no activity in Picrophilus torridus
strain DSM 9790
-
-
Manually annotated by BRENDA team
no activity in Pyrobaculum aerophilum
strain IM2
-
-
Manually annotated by BRENDA team
no activity in Pyrobaculum aerophilum IM2
strain IM2
-
-
Manually annotated by BRENDA team
no activity in Pyrococcus abyssi
strain GE5
-
-
Manually annotated by BRENDA team
no activity in Pyrococcus abyssi GE5
strain GE5
-
-
Manually annotated by BRENDA team
no activity in Pyrococcus furiosus
strain DSM 3638
-
-
Manually annotated by BRENDA team
no activity in Pyrococcus horikoshii
strain OT3
-
-
Manually annotated by BRENDA team
no activity in Pyrococcus horikoshii OT3
strain OT3
-
-
Manually annotated by BRENDA team
no activity in Sulfolobus acidocaldarius
DSM 639
-
-
Manually annotated by BRENDA team
no activity in Sulfolobus solfataricus
strain P2
-
-
Manually annotated by BRENDA team
no activity in Sulfolobus solfataricus P2
strain P2
-
-
Manually annotated by BRENDA team
no activity in Sulfolobus tokodaii
strain 7
-
-
Manually annotated by BRENDA team
no activity in Sulfolobus tokodaii 7
strain 7
-
-
Manually annotated by BRENDA team
no activity in Thermococcus kodakarensis
strain KOD1
-
-
Manually annotated by BRENDA team
no activity in Thermococcus kodakarensis KOD1
strain KOD1
-
-
Manually annotated by BRENDA team
no activity in Thermoplasma acidophilum
DSM 1728
-
-
Manually annotated by BRENDA team
no activity in Thermoplasma volcanium
strain GSS1
-
-
Manually annotated by BRENDA team
no activity in Thermoplasma volcanium GSS1
strain GSS1
-
-
Manually annotated by BRENDA team
no activity in Thermotoga maritima
-
-
-
Manually annotated by BRENDA team
enzyme belongs to the metal-containing MsrB group I
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain BY4741, enzyme MsrB
-
-
Manually annotated by BRENDA team
winter rye, cv. Halo
-
-
Manually annotated by BRENDA team
3 copies of gene msrB
-
-
Manually annotated by BRENDA team
; gene msr encodes an enzyme showing both MsrA, methionine S-oxide reductase (S-form oxidizing), and MsrB, methionine S-oxide reductase (R-form oxidizing), activity
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
enzyme belongs to the metal-containing MsrB group I
-
-
Manually annotated by BRENDA team
3 isozymes of MsrB
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-methyl 4-tolyl sulfoxide + thioredoxin
?
show the reaction diagram
-
-
-
-
?
acetyl-L-methionine (R)-sulfoxide methyl ester + thioredoxin
L-methionine methyl ester + thioredoxin disulfide + H2O
show the reaction diagram
-
the affinity of MsrB to acetyl-L-methionine (R)-sulfoxide methyl ester is higher than to L-methionine (R)-sulfoxide
-
-
?
acetyl-L-methionine-(R)-S-oxide-NHMe + thioredoxin
?
show the reaction diagram
-
-
-
-
?
calmodulin-L-methionine (R)-S-oxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrBA is able to completely reduce (i.e., repair) MetSO in the calcium regulatory protein calmodulin. The efficient repair is the coordinate activity of the two catalytic domains in the MsrBA fusion protein, which results in a 1 order of magnitude rate enhancement in comparison to those of the individual MsrA or MsrB enzyme alone
-
-
?
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
dabsyl L-methionine (R)-sulfoxide + thioredoxin
dabsyl L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
dabsyl-L-methionine (R)-sulfoxide + 1,4-dithioerythritol
dabsyl-L-methionine + 1,4-dithioerythritol disulfide + H2O
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + CDSP32
dabsyl-L-methionine + ?
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
dabsyl-L-methionine (R)-sulfoxide + glutaredoxin C4
?
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + glutaredoxin S12
?
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + glutaredoxin S12
dabsyl-L-methionine + ?
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
dabsyl-L-methionine (R)-sulfoxide + thioredoxin h1
?
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine-(R)-S-oxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine-(R)-S-oxide + dithiothreitol
dabsyl-L-methionine + DTT disulfide + H2O
show the reaction diagram
DL-methionine (R)-sulfoxide + thioredoxin
DL-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
enzyme MsrB is specific for the R-form, active on free and protein-bound methionine, the latter is bound more efficiently
-
-
?
Hsp21 L-methionine S-oxide + dithiothreitol
Hsp21 L-methionine + dithiothreitol S-oxide
show the reaction diagram
L-methionine (R)-sulfoxide + dithiothreitol
L-methionine + dithiothreitol disulfide
show the reaction diagram
L-methionine (R)-sulfoxide + dithiothreitol
L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine (R,S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide
show the reaction diagram
L-methionine sulfoxide enkephalin + thioredoxin
L-methionine enkephalin
show the reaction diagram
-
membrane-bound enzyme form Mem-R,S-Msr
-
-
?
L-methionine-(R)-S-oxide + dithioerythritol
L-methionine + dithioerythritol disulfide + H2O
show the reaction diagram
-
absolute stereospecific reduction, MsrB1 and MsrB2
-
-
?
L-methionine-(R)-S-oxide + DTT
L-methionine + DTT disulfide + H2O
show the reaction diagram
L-methionine-(R)-S-oxide + DTT
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
isozymes MsrB1, MsrB2, and MsrB3
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
N-acetyl-L-methionine (R)-sulfoxide + dithiothreitol
N-acetyl-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
-
-
-
-
?
N-acetyl-L-methionine (R)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
N-acetyl-L-methionine (R)-sulfoxide methyl ester + thioredoxin
N-acetyl-L-methionine methyl ester + thioredoxin disulfide
show the reaction diagram
-
enzyme MsrB
-
-
?
N-acetyl-L-methionine (R,S)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide
show the reaction diagram
N-acetyl-L-methionine-(R)-S-oxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
oxidized calmodulin + thioredoxin
partially reduced calmodulin + thioredoxin disulfide
show the reaction diagram
-
enzyme reduces L-methionine (R)-sulfoxide of the protein substrate
-
-
?
oxidized chloroplast signal particle protein 43 + ?
reduced chloroplast signal particle protein 43 + ?
show the reaction diagram
-
-
-
-
?
oxidized chloroplast signal particle protein 54 + ?
reduced chloroplast signal particle protein 54 + ?
show the reaction diagram
-
-
-
-
?
peptide-L-methionine-(R)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
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
-
-
?
protein L-methionine (R)-sulfoxide + thioredoxin
protein L-methionine + thioredoxin disulfide
show the reaction diagram
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine (R)-S-oxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
Met sulfoxide residues in an Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
protein-L-methionine (R)-sulfoxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine-(R)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrB is specific for the R-form, the membrane-associated isozyme reduces both R- and S-stereoisomers of methionine sulfoxide, N-acetylmethionine sulfoxide, and D-Ala-Met-enkephalin
-
-
?
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide
show the reaction diagram
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
calmodulin-L-methionine (R)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
Hsp21 L-methionine S-oxide + dithiothreitol
Hsp21 L-methionine + dithiothreitol S-oxide
show the reaction diagram
-
chloroplast-localized small heat shock protein, repair function for heat shock protein Hsp21 by restoring the structure, which is crucial for cellular resistance to oxidative stress, the enzyme can protect the chaperone-like activity of Hsp21
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine (R,S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide
show the reaction diagram
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
peptide-L-methionine-(R)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
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
-
-
?
protein L-methionine (R)-sulfoxide + thioredoxin
protein L-methionine + thioredoxin disulfide
show the reaction diagram
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine (R)-S-oxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
Q78J03
Met sulfoxide residues in an Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
protein-L-methionine (R)-sulfoxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
-
type B enzyme CBS1 is stereospecific for the R-stereomer of methionine residues of peptides and proteins
-
-
?
protein-L-methionine-(R)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrB is specific for the R-form, the membrane-associated isozyme reduces both R- and S-stereoisomers of methionine sulfoxide, N-acetylmethionine sulfoxide, and D-Ala-Met-enkephalin
-
-
?
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide
show the reaction diagram
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithioerythritol
-
DTE
dithiothreitol
NADPH
-
membrane-bound enzyme form Mem-R,S-Msr
thioredoxin
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
with Zn2+ in a ratio of 1 mol per mole of enzyme, tight metal binding
selenium
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-carboxy 4-nitrobenzenethiol
dimedone
H2O2
-
1 mM, 40% deactivation of MSRB1
L-Methionine sulfone
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14 - 2.2
acetyl-L-methionine (R)-S-oxide methyl ester
0.00021
CDSP32
-
pH 8.0, 37C, cosubstrate: dabsyl-L-methionine (R)-sulfoxide, MSRB1 activity
-
0.0091 - 2
dithiothreitol
0.0068
glutaredoxin C4
-
isoform MSRB1 wild type enzyme
-
0.00053
glutaredoxin S12
-
pH 8.0, 37C, cosubstrate: dabsyl-L-methionine (R)-sulfoxide, MSRB1 activity
-
1.451 - 67
L-methionine (R)-sulfoxide
56
L-methionine (R,S)-sulfoxide
-
MsrB activity of PILB, pH 8.0, 25C
0.054 - 1.3
L-methionine-(R)-S-oxide
0.049
N-acetyl-L-methionine (R)-sulfoxide
-
isoform MSRB2, pH and temperature not specified in the publication; isoform MSRB4, pH and temperature not specified in the publication
0.026 - 7
thioredoxin
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
Abz-VAA
Escherichia coli
-
in vitro, substrate free L-methionine (R)-sulfoxide
-
0.035
CDSP32
Arabidopsis sp.
-
pH 8.0, 37C, cosubstrate: dabsyl-L-methionine (R)-sulfoxide, MSRB1 activity
-
0.002 - 0.075
dabsyl-L-methionine (R)-sulfoxide
0.09
dithiothreitol
Solanum lycopersicum
Q9C8M2
recombinant enzyme, in 50 mM Tris-HCl, pH 8.0, at 37C
0.02 - 0.48
glutaredoxin C4
0.03 - 0.58
glutaredoxin S12
0.13 - 2.86
L-methionine (R)-sulfoxide
2.8
L-methionine (R,S)-sulfoxide
Neisseria meningitidis
-
MsrB activity of PILB, pH 8.0, 25C
0.002 - 0.83
L-methionine-(R)-S-oxide
0.24 - 2.04
N-acetyl-L-methionine (R)-sulfoxide
1.28
thioredoxin h1
Arabidopsis thaliana
-
isoform MSRB2 wild type enzyme
-
additional information
additional information
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10
dithiothreitol
Solanum lycopersicum
Q9C8M2
recombinant enzyme, in 50 mM Tris-HCl, pH 8.0, at 37C
45
73.4
glutaredoxin C4
Arabidopsis thaliana
-
isoform MSRB1 wild type enzyme
11994
0.09 - 1.4
L-methionine (R)-sulfoxide
5 - 42
N-acetyl-L-methionine (R)-sulfoxide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000029
-
wild-type strain RN450, substrate L-methionine (R)-sulfoxide