Structural basis for the tight binding inhibition of <i>E. coli</i> CTP synthase inhibition by gemcitabine and its analogues
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
CTP synthase (CTPS) is a vital metabolic enzyme which controls the pyrimidine nucleotide pool by converting UTP into CTP with the use of ATP and ammonia. The E coli. variant is tightly regulated by the available nucleotides, where it is allosterically modulated by GTP and CTP. CTP binding can induce inhibitory filament formation, whereas the human isozyme forms active filaments upon UTP binding. Due to the in vivo importance of CTPS, variable regulatory mechanism across species, and previous data suggesting it is vital to the maintenance of various disease states, selective inhibition of CTPS may be a fruitful avenue to develop treatments for some of these illnesses. Most recently, a series of fluorinated CTP analogues were characterized for their inhibition against CTPS. Of these molecules, a doublely fluorinated at the 2' position of the ribose moiety had an at least 30x increased inhibition over its monofluorinated counterparts. Here, we determined the crystal structures of the various fluorinated inhibitors of CTPS to determine the molecular interactions and conformational changes contributing to the potent inhibition of the enzyme by these nucleotide analogues.
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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 | 0.000 |
| 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 | 0.000 |
| 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