Pretransfer Editing in Threonyl-tRNA Synthetase: Roles of Differential Solvent Accessibility and Intermediate Stabilization
Bibliographic record
Abstract
Aminoacyl-tRNA synthetases (aaRSs) catalyze the activation of the corresponding amino acids and attachment to their cognate tRNAs with extremely high fidelity due to pre- and post-transfer editing processes. We have computationally elucidated a pretransfer editing mechanism in yeast mitochondrial threonyl-tRNA synthetase (MST1) via the combined application of classical molecular dynamics and QM/MM-MD free energy calculations. It is concluded that the pretransfer editing mechanism against seryl-AMP occurs in two steps via an oxyanion intermediate. Importantly, its formation is central to, within the aminoacylation active site, the differential rates at which threonyl-tRNA synthetase (ThrRS) is able to hydrolyze its cognate threonyl-AMP and noncognate seryl-AMP substrates. More specifically, in contrast to that observed when threonyl-AMP is bound in the ThrRS active site, the binding of seryl-AMP enables a greater number of waters to permeate into the active site. This results in greater stabilization of the seryl-AMP derived oxyanion intermediate via hydrogen bonding such that it is thermodynamically more stable by 7–10 kcal mol –1 than is the case for threonyl-AMP. Moreover, the barrier associated with the first step of the hydrolytic pretransfer mechanism is less for seryl-AMP than for threonyl-AMP by 4–10 kcal mol –1 . These results help to explain the preferential degradation of noncognate seryl-AMP over threonyl-AMP by ThrRS.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".