Information on EC 1.8.4.11 - peptide-methionine (S)-S-oxide reductase and Organism(s) Escherichia coli and UniProt Accession P0A744

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This record set is specific for:
Escherichia coli
UNIPROT: P0A744


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


The taxonomic range for the selected organisms is: Escherichia coli

EC NUMBER
COMMENTARY hide
1.8.4.11
-
RECOMMENDED NAME
GeneOntology No.
peptide-methionine (S)-S-oxide reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-methionine (S)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
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].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-L-methionine-(S)-S-oxide-NHMe + thioredoxin
acetyl-L-methionine-NHMe + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
(S)-methyl 4-tolyl sulfoxide + thioredoxin
?
show the reaction diagram
-
FMsr is specific for the S-isomer
-
-
?
calmodulin-L-methionine (S)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (S)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
FMsr is specific for the S-isomer
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
the membrane-associated isozyme reduces both R- and S-stereoisomers of methionine sulfoxide in proteins
-
-
?
L-methionine (S)-sulfoxide + 2 dithiothreitol
L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
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-(S)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
N-acetyl-L-methionine (R)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
the membrane-associated isozyme reduces both R- and S-stereoisomer of methionine sulfoxide in proteins
-
-
?
N-acetyl-L-methionine (R,S)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide
show the reaction diagram
-
membrane-bound enzyme form Mem-R,S-Msr
-
-
?
N-acetyl-L-methionine (S)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA and soluble isozyme MsrA1 are specific for the S-form, the membrane-associated isozyme reduces both R- and S-stereoisomers
-
-
?
N-acetyl-L-methionine-(S)-S-oxide + DTT
N-acetyl-L-methionine + DTT disulfide + H2O
show the reaction diagram
-
stereospecific reduction
-
-
?
N-acetyl-L-methionine-(S)-S-oxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
stereospecific reduction
-
-
?
oxidized calmodulin + thioredoxin
partially reduced calmodulin + thioredoxin disulfide
show the reaction diagram
-
enzyme reduces L-methionine (S)-sulfoxide of the protein substrate
-
-
?
peptide-L-methionine-(S)-S-oxide + DTT
peptide-L-methionine + DTT disulfide + H2O
show the reaction diagram
peptide-L-methionine-(S)-S-oxide + thioredoxin
peptide-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
protein-L-methionine (S)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA and the soluble isozyme MsrA1 are specific for the S-form, the membrane-associated isozyme reduces both R- and S-stereoisomers of methionine sulfoxide, N-acetylmethionine sulfoxide, and D-Ala-Met-enkephalin
-
-
?
ribosomal protein L12-L-methionine (S)-sulfoxide + thioredoxin
ribosomal protein L12-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide
show the reaction diagram
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide + H2O
show the reaction diagram
Tyr-Gly-Gly-Phe-L-methionine-(S)-S-oxide + DTT
Tyr-Gly-Gly-Phe-L-methionine + DTT disulfide + H2O
show the reaction diagram
-
oxidized Met-enkephalin
-
-
?
Tyr-Gly-Gly-Phe-L-methionine-(S)-S-oxide + thioredoxin
Tyr-Gly-Gly-Phe-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
oxidized Met-enkephalin
-
-
?
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 (S)-sulfoxide + thioredoxin
calmodulin-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
L-methionine (S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine-(S)-S-oxide + thioredoxin
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
protein-L-methionine (S)-sulfoxide + thioredoxin
protein-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
MsrA and the soluble isozyme MsrA1 are specific for the S-form, the membrane-associated isozyme reduces both R- and S-stereoisomers of methionine sulfoxide, N-acetylmethionine sulfoxide, and D-Ala-Met-enkephalin
-
-
?
ribosomal protein L12-L-methionine (S)-sulfoxide + thioredoxin
ribosomal protein L12-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide
show the reaction diagram
-
activation of a methionine sulfoxide-containing prodrug, activity with membrane-bound enzyme form Mem-R,S-Msr and MsrA
activated drug which inhibits cyclooxygenase 1 and 2 and exhibiting anti-inflammatory activity
-
?
sulindac + thioredoxin
sulindac sulfide + thioredoxin disulfide + H2O
show the reaction diagram
-
activation of the antiinflammatory drug with anti-tumorigenic activity, which acts via inhibition of cyclooxygenases 1 and 2
-
-
?
Tyr-Gly-Gly-Phe-L-methionine-(S)-S-oxide + thioredoxin
Tyr-Gly-Gly-Phe-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
oxidized Met-enkephalin
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
thioredoxin
-
-
dithiothreitol
NADPH
-
membrane-bound enzyme form Mem-R,S-Msr
thioredoxin
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KCl
-
enzyme prefers high ionic strength, activation
Mg2+
-
activates
Na2SO4
-
enzyme prefers high ionic strength, activation
NaCl
-
enzyme prefers high ionic strength, activation
NaF
-
enzyme prefers high ionic strength, activation
selenium
-
selenocysteine-containing
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-carboxy 4-nitrobenzenethiol
-
binds specifically to the sulfenic acid reaction intermediate
dimedone
-
binds specifically to the sulfenic acid reaction intermediate
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.19
thioredoxin
-
mutant C86S/C206S, pH 8.0, 25C
0.12 - 1.9
L-methionine (S)-sulfoxide
0.01
thioredoxin
-
pH 8.0, 25C, substrate L-methionine (S)-sulfoxide
additional information
additional information
-
kinetic mechanism
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.088
thioredoxin
-
mutant C86S/C206S, pH 8.0, 25C
3.7
L-methionine (S)-sulfoxide
-
pH 8.0, 25C, cofactor thioredoxin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00009
-
enzyme form Mem-R,S-Msr, substrate sulindac
0.00019
0.0004
-
membrane vesicles, substrate N-acetyl-L-methionine-(R)-sulfoxide
0.00044
-
MsrA, substrate N-acetyl-L-methionine-(S)-sulfoxide
0.00047
-
membrane vesicles, substrate N-acetyl-L-methionine-(S)-sulfoxide
0.0018
-
wild-type strain, substrate L-methionine (S)-sulfoxide
0.33
-
in vitro, substrate free L-methionine (R)-sulfoxide
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
soluble isozyme MsrA1
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25000
-
x * 25000, MsrA
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 25000, MsrA
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
15-50 mg/ml purified recombinant MsrA in 50 mM Tris-HCl, pH 8.0, 2 mM EDTA, and 10 mM DTT, hanging drop vapour diffusion method, droplet size is 0.004-0.008 ml, equal volumes of protein and precipitant solution, X-ray diffraction structure determination and analysis at 1.9 A resolution
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme by ammonium sulfate fractionation, dialysis, anion exchange chromatography, and gel filtration
-
partially
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)
-
recombinant MsrA
-
recombinant MsrA from strain B834(DE3)
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; gene msrA, DNA and amino acid sequence determination and analysis, recombinant expression, functional overexpression of MsrB from gene msrB or yeaA
-
gene msrA
-
gene msrA, expression in an msrA-deficient Escherichia coli mutant strain Tn903::msrA conferring resistance against oxidative damage from reactive nitrogen intermediates
-
gene msrA, expression in Escherichia coli strain BL21(DE3) as His-tagged enzyme
-
gene msrA, expression in strain B834(DE3)
-
gene msrA, located in the chromosome at 95.69 min, respectively, recombinant expression of msrA, regulation mechanism of gene expression, overview
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C86S/C206S
-
KM and kcat value are 19fold higher and 40fold slower compared to wild type, respectively. The Cys198-Cys206 disulfide bond is rather reduced by thioredoxin under steady-state conditions instead of the Cys51-Cys198 disulfide bond
C198S
-
MsrA mutant, mutation of one recycling Cys to Ser results in an enzyme forming methionine but without recycling activity, probably due to formation of a nonproductive complex between sulfenic intermediate and thioredoxin
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
with MsrA adsorbed on glassy carbon and boron doped diamond electrodes surface, the first step reaction step corresponds to the oxidation of tyrosine and tryptophan residues and occurs for the same potential. The second step is histidine oxidation, and the third, at higher potentials, the second tryptophan oxidation. MsrA adsorbs on the hydrophobic carbon electrode surface preferentially through the three hydrophobic domains, C1, C2 and C3, which contain the tyrosine, tryptophan and histidine residues
synthesis
-
enzyme can be useful in the development and action of anti-cancer and anti-inflammation drugs