Reversible inhibition of the ClpP protease via an N-terminal conformational switch
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Significance ClpP is a protease that degrades damaged or misfolded proteins. Consistent with its critical role in maintaining cellular homeostasis, inhibiting and dysregulating ClpP function has shown promise in fighting antibiotic resistance and in targeting cancer cells in acute myeloid leukemia. Here we identify a conformational switch in ClpP that, upon mutagenesis, leads to a catalytically inactive structure that can be reactivated through the binding of small-molecule activators. This functional hotspot therefore represents a drug target for allosteric inhibition of ClpP. The combination of methyl–transverse relaxation-optimized spectroscopy (TROSY) NMR, cryo-EM, and molecular simulation methods employed here provides a detailed characterization of ClpP along with the promise of crucial insights into the structure–function relationship of molecular machines in general.
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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 | 0.001 | 0.000 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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