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Information on EC 1.8.4.12 - peptide-methionine (R)-S-oxide reductase and Organism(s) Neisseria gonorrhoeae and UniProt Accession P14930
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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: Neisseria gonorrhoeae
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
MsrA/B
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
catalytic mechanism involves the formation of a sulfenic acid intermediate
-
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
mechanism, active site structure, conserved catalytic Cys residues are essential for activity, Cys residue recycling, overview
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
reaction mechanism, modeling of substrate binding at the active site, Cys444 and Cys495 are involved
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 activity of the tandem domains of PilB, the MsrB domain alone does not utilize the S-isomer
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form
-
-
?
N-acetyl-L-methionine (R,S)-sulfoxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide
-
enzyme MsrA/B shows both MsrA and MsrB activity, free and protein-bound methionine
-
-
?
N-acetyl-L-methionine-(R)-S-oxide + thioredoxin
N-acetyl-L-methionine + thioredoxin disulfide + H2O
-
-
-
-
?
L-methionine (R,S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide
-
the enzyme protects cells against oxidative damage and plays a role in age-related misfunctions
-
-
?
L-methionine (R,S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide
-
enzyme MsrA/B shows both MsrA and MsrB activity, free and protein-bound methionine
-
-
?
additional information
?
-
the tandem domains of PilB also possess MsrA activity utilizing L-methionine (S)-sulfoxide as substrate, the MsrA domain alone does very poorly utilize the R-isomer
-
-
?
additional information
?
-
-
the tandem domains of PilB also possess MsrA activity utilizing L-methionine (S)-sulfoxide as substrate, the MsrA domain alone does very poorly utilize the R-isomer
-
-
?
additional information
?
-
-
enzyme acts on free and protein-bound methionine
-
-
?
additional information
?
-
-
substrate specificity and activity of MsrB/PilB in comparison to MsrA, overview
-
-
?
additional information
?
-
-
PilB affects the survival of the organism to reactive oxygen species, PilB is not involved in piliation, pilin production, or adherence
-
-
?
additional information
?
-
-
The thioredoxin domain of PilB can use electrons from DsbD to reduce downstream methionine sulfoxide reductases, overview
-
-
?
additional information
?
-
-
the bifunctional enzyme catalyzes both reactions of MsrB or PilB, EC 1.8.4.12, and of MsrA or PilA, EC 1.8.4.11, the catalytic sites for the two different activities are localized separately on the enzyme molecule, overview
-
-
?
additional information
?
-
-
the bifunctional enzyme catalyzes both reactions of MsrB or PilB, EC 1.8.4.12, and of MsrA or PilA, EC 1.8.4.11, the catalytic sites for the two different activities are localized separatly on the enzyme molecule, overview
-
-
?
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
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
-
MsrB is specific for the R-form
-
-
?
L-methionine (R,S)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide
-
the enzyme protects cells against oxidative damage and plays a role in age-related misfunctions
-
-
?
additional information
?
-
-
enzyme acts on free and protein-bound methionine
-
-
?
additional information
?
-
-
PilB affects the survival of the organism to reactive oxygen species, PilB is not involved in piliation, pilin production, or adherence
-
-
?
additional information
?
-
-
The thioredoxin domain of PilB can use electrons from DsbD to reduce downstream methionine sulfoxide reductases, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
thioredoxin
-
PilB contains an N-terminal thioredoxin-like domain, the NT domain, fused to the MsrA and MSrB domains, structure overview
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.075
purified recombinant MsrA/MsrB tandem domain, substrate L-methionine (R)-sulfoxide
0.11
purified recombinant MsrB domain alone, substrate L-methionine (R)-sulfoxide
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
enzyme contains MsrA and MsrB domains; PilB enzyme has 2 catalytic domains showing MsrA, methionine S-oxide reductase (S-form oxidizing), and MsrB, methionine S-oxide reductase (R-form oxidizing), activity, respectively, the MsrB domain contains a selenomethionine at position 39
SwissProt
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
analysis of three-dimensional structure and active site structure
additional information
enzyme domain and active site structure, MsrB domain comprises residues 375-522, overview
additional information
-
enzyme domain and active site structure, MsrB domain comprises residues 375-522, overview
additional information
-
the 2 enzyme activities, MsrA and MsrB, form domains of a single polypeptide together with a third thioredoxin-like domain
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant detagged MsrB domain containing SeMet39, hanging drop vapour-diffusion method, 15 mg/ml protein in 20 mM Tris, pH 8.5, 10% v/v glycerol, against a well solution containing 0.1 M sodium cacodylate, pH 6.5, 30% w/v PEG 4000, room temperature, X-ray diffraction structure determination and analysis at 1.8 A resolution, modeling
purified recombinant PilB mutant L38M/L41M, vapour diffusion method, 30 mg/ml protein in 20 mM HEPES, pH 7.5, and 100 mM NaCl, is mixed with well solution containing 0.1 M MES, pH 6.5, 0.2 M ammonium sulfate, 26% PEG 2000 monomethylester, and 25% glycerol, X-ray diffraction structure determination and analysis at 1.6 A resolution, multiwavelength anomalous dispersion at -170°C
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
L38M/L41M
-
site-directed mutagenesis, mutation of the NT domain of PilB, thioredoxin binding structure, crystal structure analysis, overview
additional information
additional information
-
mutant strains produce a truncated version of fused MsrA/MsrB with increased sensitivity to H2O2 and superoxide anions
additional information
-
construction of truncated PilB domain forms, which show decreased survival of the organism to reactive oxygen species, the mutations do not affect piliation, pilin production, or adherence, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged full length tandem enzyme, MsrA, and MsrB domains from Escherichia coli, tags are removed by thrombin digestion
recombinant His-tagged PilB forms in Escherichia coli strain Xl-1 blue by nickel affinity chromatography
-
recombinant N-terminally His-tagged full-length PilB and MsrB domain variants from Escherichia coli by nickel affinity chromatography followed by cleavage of the His-Tag through thrombin, followed by gel filtration and ion exchange chomatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of the full length tandem enzyme, the MsrA, and the MsrB domains, all His-tagged, in Escherichia coli
gene pilB, expression of N-terminally His-tagged full-length wild-type and mutant PilB and MsrB domain variants in Escherichia coli
-
gene pilB, transposon insertion, truncated PilB enzyme forms of the enzyme lacking the MsrA domain from strain MS11, variant VD300, overexpression of the His-tagged PilB forms in Escherichia coli strain Xl-1 blue
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
Ezraty, B.; Aussel, L.; Barras, F.
Methionine sulfoxide reductases in prokaryotes
Biochim. Biophys. Acta
1703
221-229
2005
Aggregatibacter actinomycetemcomitans, Bacillus subtilis, Dickeya chrysanthemi, Escherichia coli, Helicobacter pylori, Mycobacterium tuberculosis, Mycolicibacterium smegmatis, Neisseria gonorrhoeae, Neisseria meningitidis, no activity in Aquifex aeolicus, no activity in Thermotoga maritima, Sinorhizobium meliloti, Staphylococcus aureus, Vibrio cholerae serotype O1
Kauffmann, B.; Aubry, A.; Favier, F.
The three-dimensional structures of peptide methionine sulfoxide reductases: current knowledge and open questions
Biochim. Biophys. Acta
1703
249-260
2005
Caulobacter vibrioides, Drosophila melanogaster, Escherichia coli, Neisseria meningitidis, Pseudomonas aeruginosa, Synechococcus elongatus, Neisseria gonorrhoeae (P14930)
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)
Brot, N.; Collet, J.F.; Johnson, L.C.; Jonsson, T.J.; Weissbach, H.; Lowther, W.T.
The thioredoxin domain of Neisseria gonorrhoeae PilB can use electrons from DsbD to reduce downstream methionine sulfoxide reductases
J. Biol. Chem.
281
32668-32675
2006
Neisseria gonorrhoeae
Skaar, E.P.; Tobiason, D.M.; Quick, J.; Judd, R.C.; Weissbach, H.; Etienne, F.; Brot, N.; Seifert, H.S.
The outer membrane localization of the Neisseria gonorrhoeae MsrA/B is involved in survival against reactive oxygen species
Proc. Natl. Acad. Sci. USA
99
10108-10113
2002
Neisseria gonorrhoeae, Neisseria gonorrhoeae MS11
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