Crystal Structures of Human Pantothenate Kinases
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Bibliographic record
Abstract
Pantothenate kinase (PanK) catalyzes the first step in CoA biosynthesis and there are three human genes that express four isoforms with highly conserved catalytic core domains. Here we report the homodimeric structures of the catalytic cores of PanK1alpha and PanK3 in complex with acetyl-CoA, a feedback inhibitor. Each monomer adopts a fold of the actin kinase superfamily and the inhibitor-bound structures explain the basis for the allosteric regulation by CoA thioesters. These structures also provide an opportunity to investigate the structural effects of the PanK2 mutations that have been implicated in neurodegeneration. Biochemical and thermodynamic analyses of the PanK3 mutant proteins corresponding to PanK2 mutations show that mutant proteins with compromised activities and/or stabilities correlate with a higher incidence of the early onset of disease.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it