MsrA (PA5018) is the peptide methionine (S)-sulfoxide reductase of Pseudomonas aeruginosa (EC 1.8.4.11), a cytoplasmic repair enzyme that reduces the S epimer of methionine sulfoxide in oxidised proteins (and free methionine sulfoxide) back to methionine, using thioredoxin as the reductant and a catalytic cysteine. It acts alongside MsrB, which reduces the R epimer. msrA is expressed constitutively at a high level throughout growth, unlike the oxidant-inducible msrB. msrA mutants are more sensitive to hypochlorite and H2O2, are paradoxically more resistant to paraquat, and are attenuated in a Drosophila infection model.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000019085, seeded by E. coli MsrA and eukaryotic MsrAs. Bacterial MsrA has no signal peptide or TM segment and acts in the cytoplasm. Reason: Correct location for a soluble bacterial repair enzyme; no more specific term is warranted. Supporting Evidence: file:PSEAE/msrA/msrA-uniprot.txt Belongs to the MsrA Met sulfoxide reductase family. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA term. Reason: Entailed by GO:0034599 cellular response to oxidative stress (is_a), accepted below. |
| GO:0008113 peptide-methionine (S)-S-oxide reductase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000019085 with many IDA/EXP seeds (E. coli, M. tuberculosis, human, rat, yeast, plant MsrAs). Reason: Core activity of the MsrA family; HAMAP and Pfam membership agree. Supporting Evidence: file:PSEAE/msrA/msrA-uniprot.txt Belongs to the MsrA Met sulfoxide reductase family. |
| GO:0008113 peptide-methionine (S)-S-oxide reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mapping from MsrA family signatures. Reason: Consistent with the IBA row. Supporting Evidence: file:PSEAE/msrA/msrA-uniprot.txt Belongs to the MsrA Met sulfoxide reductase family. |
| GO:0033744 L-methionine (S)-S-oxide reductase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reduction of free L-Met-(S)-SO, an activity of MsrA-family enzymes demonstrated for several seeds (e.g. E. coli MsrA). Reason: Genuine secondary activity of MsrA; the protein-repair activity is the core function. Supporting Evidence: file:PSEAE/msrA/msrA-uniprot.txt Belongs to the MsrA Met sulfoxide reductase family. |
| GO:0033744 L-methionine (S)-S-oxide reductase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea mapping of the free-methionine reaction. Reason: Same claim as the IBA row; consistent action. |
| GO:0034599 cellular response to oxidative stress | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000019085. Seeds include the PseudoCAP IMP on Q9HUF1 itself (expected, not circular) and independent IMP seeds from yeast, fission yeast, Arabidopsis and Aspergillus. The IBD stands without this seed. Reason: MsrA repairs oxidised methionine residues, a direct part of the oxidative stress response. Supporting Evidence: PMID:23687271 rendered the mutants less resistant than the parental PAO1 strain to oxidants such as NaOCl |
| GO:0034599 cellular response to oxidative stress | IMP PMID:23687271 Gene expression and physiological role of Pseudomonas aerugi... | ACCEPT | Summary: PseudoCAP seed row. Deletion lowers NaOCl and H2O2 resistance and is complemented by plasmid msrA (full text read). Reason: Seed verdict SOUND. Supporting Evidence: PMID:23687271 pBBR msrA and pBBR msrB plasmids fully complemented the NaOCl-sensitive phenotypes of msrA and msrB mutants to resistance levels attained by the parental strain |
| GO:1901530 response to hypochlorite | IMP PMID:23687271 Gene expression and physiological role of Pseudomonas aerugi... | ACCEPT | Summary: msrA mutant is NaOCl-sensitive and complemented by plasmid msrA. Reason: Hypochlorite is the oxidant with the clearest msrA phenotype; MsrA repairs HOCl-oxidised methionine. Supporting Evidence: PMID:23687271 pBBR msrA and pBBR msrB plasmids fully complemented the NaOCl-sensitive phenotypes of msrA and msrB mutants to resistance levels attained by the parental strain |
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Download this section (compressed HTML)Q: Why does loss of msrA increase paraquat resistance in P. aeruginosa, and is this linked to compensatory induction of other stress defences?
Experiment: Measure MsrA activity on Met-(S)-SO-containing peptides and free Met-(S)-SO with purified PA MsrA and thioredoxin, to confirm the inferred activities.
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