PST2
S. cerevisiae
flavodoxin-like fold family protein
What the model saw
Gene: PST2 Organism: Saccharomyces cerevisiae Known functions: flavodoxin-like fold family protein. FMN binding. NAD(P)H dehydrogenase (quinone) activity. identical protein binding. oxidoreductase activity. protein binding.
View unredacted entry
flavodoxin-like fold family protein. FMN binding. NAD(P)H dehydrogenase (quinone) activity. identical protein binding. oxidoreductase activity. protein binding.
Solver output
PST2 encodes a flavodoxin-like fold protein with FMN binding and NAD(P)H:quinone oxidoreductase activity, placing it in the family of quinone reductases that protect against oxidative stress by performing obligate two-electron reductions of quinones, thereby preventing the one-electron redox cycling that generates reactive oxygen species (ROS). By channeling quinone reduction through a safe two-electron pathway, PST2 reduces mitochondrial and cytosolic ROS burden, which is a well-established pro-longevity mechanism in yeast. Its close paralog YCP4 and the broader flavodoxin/WrbA family in other organisms are associated with oxidative stress resistance and extended lifespan. The NAD(P)H-dependent activity also links PST2 to cellular redox homeostasis, supporting mitochondrial electron transport chain efficiency and reducing oxidative damage to macromolecules.
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 predicted PST2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning was plausible on the surface — it correctly identified PST2's biochemical functions (flavodoxin-like fold, FMN binding, NAD(P)H:quinone oxidoreductase activity) and constructed a logical argument about ROS reduction leading to extended lifespan. However, the conclusion was wrong. In yeast, PST2 deletion studies apparently show extended lifespan, meaning PST2 normally acts to limit longevity (anti_longevity). The model failed to consider that some oxidoreductases in yeast can have anti-longevity effects, perhaps by consuming NAD(P)H or through other mechanisms that reduce stress resistance signaling. The model's confidence of 0.62 was moderate but still committed to the wrong answer. The mechanistic reasoning, while internally consistent, led to the wrong prediction and doesn't reflect the actual biology as catalogued in GenAge.
Raw API responses
solver
{
"reasoning": "PST2 encodes a flavodoxin-like fold protein with FMN binding and NAD(P)H:quinone oxidoreductase activity, placing it in the family of quinone reductases that protect against oxidative stress by performing obligate two-electron reductions of quinones, thereby preventing the one-electron redox cycling that generates reactive oxygen species (ROS). By channeling quinone reduction through a safe two-electron pathway, PST2 reduces mitochondrial and cytosolic ROS burden, which is a well-established pro-longevity mechanism in yeast. Its close paralog YCP4 and the broader flavodoxin/WrbA family in other organisms are associated with oxidative stress resistance and extended lifespan. The NAD(P)H-dependent activity also links PST2 to cellular redox homeostasis, supporting mitochondrial electron transport chain efficiency and reducing oxidative damage to macromolecules.",
"confidence": 0.62,
"key_pathways": [
"NAD(P)H:quinone oxidoreductase / quinone detoxification",
"ROS scavenging and redox homeostasis",
"FMN-dependent oxidoreductase activity"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted PST2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning was plausible on the surface — it correctly identified PST2's biochemical functions (flavodoxin-like fold, FMN binding, NAD(P)H:quinone oxidoreductase activity) and constructed a logical argument about ROS reduction leading to extended lifespan. However, the conclusion was wrong. In yeast, PST2 deletion studies apparently show extended lifespan, meaning PST2 normally acts to limit longevity (anti_longevity). The model failed to consider that some oxidoreductases in yeast can have anti-longevity effects, perhaps by consuming NAD(P)H or through other mechanisms that reduce stress resistance signaling. The model's confidence of 0.62 was moderate but still committed to the wrong answer. The mechanistic reasoning, while internally consistent, led to the wrong prediction and doesn't reflect the actual biology as catalogued in GenAge.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}