Bibliographic record
Abstract
The aminoglycoside phosphotransferase (APH(3')-IIIa) kinases form a clinically central group of antibiotic-resistant enzymes. Computationally, we have studied the catalytic mechanism of the APH(3')-IIIa enzyme at the atomic-level. The proposed reaction mechanism involves protonation of Asp190 by the kanamycin 3'-hydroxyl group mediated through an explicit neighboring water molecule, which leads to a simultaneous nucleophilic attack on the γ-phosphate of the ATP by the deprotonated kanamycin 3'-hydroxyl group. The second step is a proton abstraction from the protonated Asp190 to the phosphate group of the phosphorylated kanamycin mediated by an explicit water molecule. The calculated Gibbs energy of activation (Δ<i>G</i><sup>⧧</sup>) of the rate-determining step for the phosphorylation reaction is 77 kJ mol<sup>-1</sup> at the M06-2X/6-311++G(2df,p)//ONIOM(M06-2X/6-31+G(d):HF/6-31G(d)) level of theory. This study has provided a new understanding of the APH(3')-IIIa catalytic mechanism that agrees with the available experimental data (Δ<i>G</i><sup>⧧</sup> = 75 ± 4 kJ mol<sup>-1</sup>) and could provide a starting point for the rational design of mechanism-based inhibitors of aminoglycoside modifying enzyme to circumvent antibiotic resistance.
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 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".