Bibliographic record
Abstract
Proline is an essential precursor for protein synthesis. As the only secondary amino acid in proteins, it plays an important role in kinking and rigidifying polypeptide backbones. The pathway for synthesis of proline in most organisms begins with phosphorylation of L-glutamate to gamma-glutamyl phosphate (GP) by glutamate 5-kinase (ProB). GP is subsequently reduced to glutamyl semialdehyde by gamma-glutamyl phosphate reductase (ProA). A striking feature of this ancient pathway is that GP is unstable, rapidly cyclizing to 5-oxoproline. For decades, it has been assumed that channeling of GP between the active sites of ProB and ProA prevents cyclization. Despite the appeal of this idea, the experimental evidence is either not convincing or, in our hands, not reproducible. We have explored an alternative hypothesis inspired by the report that ProB-GFP and ProA-GFP localize to the poles in E. coli. Colocalization of ProB and ProA at the poles would increase the probability that GP would encounter a ProA active site before it had a chance to cyclize. However, we found that localization of ProB-GFP and ProA-GFP to the poles is an artifact of the fusion of the proteins to GFP, which can cause aggregation and localization to the poles due to nucleoid exclusion. We are currently reassessing the channeling hypothesis by testing whether alterations in the surfaces of ProB and ProA that would be expected to disrupt a physical interaction have adverse consequences in vivo and in vitro. This work was funded by the National Institute for General Medical Sciences.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.004 | 0.004 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.055 | 0.034 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".