(unnamed)
S. cerevisiae
L-methionine (R)-S-oxide reductase
What the model saw
Gene: Organism: Saccharomyces cerevisiae Known functions: L-methionine (R)-S-oxide reductase. L-methionine (R)-S-oxide reductase activity.
View unredacted entry
L-methionine (R)-S-oxide reductase. L-methionine (R)-S-oxide reductase activity.
Solver output
L-methionine (R)-S-oxide reductase (MsrB in yeast, encoded by YCL033C/MXR2) catalyzes the reduction of the R-stereoisomer of methionine sulfoxide back to methionine, directly reversing oxidative damage to this amino acid. Methionine residues in proteins are highly susceptible to reactive oxygen species (ROS)-mediated oxidation, and the methionine sulfoxide reductase (Msr) system serves as a critical antioxidant repair mechanism. By restoring oxidized methionines in proteins, this enzyme helps maintain proteostasis and reduces the accumulation of oxidatively damaged proteins. In yeast, overexpression of Msr enzymes has been linked to extended replicative and chronological lifespan, while their loss accelerates aging phenotypes. This function maps most closely to the loss-of-proteostasis hallmark, as it directly repairs oxidative protein damage that would otherwise lead to protein dysfunction and aggregation.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies the gene as encoding L-methionine (R)-S-oxide reductase (MsrB/MXR2 in yeast), explains the role in reversing oxidative damage to methionine residues in proteins, connects this to proteostasis maintenance and ROS defense, and accurately notes that Msr overexpression extends lifespan in yeast while loss accelerates aging. The key pathways identified are all relevant and accurate.
Raw API responses
solver
{
"reasoning": "L-methionine (R)-S-oxide reductase (MsrB in yeast, encoded by YCL033C/MXR2) catalyzes the reduction of the R-stereoisomer of methionine sulfoxide back to methionine, directly reversing oxidative damage to this amino acid. Methionine residues in proteins are highly susceptible to reactive oxygen species (ROS)-mediated oxidation, and the methionine sulfoxide reductase (Msr) system serves as a critical antioxidant repair mechanism. By restoring oxidized methionines in proteins, this enzyme helps maintain proteostasis and reduces the accumulation of oxidatively damaged proteins. In yeast, overexpression of Msr enzymes has been linked to extended replicative and chronological lifespan, while their loss accelerates aging phenotypes. This function maps most closely to the loss-of-proteostasis hallmark, as it directly repairs oxidative protein damage that would otherwise lead to protein dysfunction and aggregation.",
"confidence": 0.82,
"key_pathways": [
"methionine sulfoxide reductase (Msr) repair pathway",
"oxidative stress response / ROS detoxification",
"protein oxidative damage repair"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies the gene as encoding L-methionine (R)-S-oxide reductase (MsrB/MXR2 in yeast), explains the role in reversing oxidative damage to methionine residues in proteins, connects this to proteostasis maintenance and ROS defense, and accurately notes that Msr overexpression extends lifespan in yeast while loss accelerates aging. The key pathways identified are all relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}