Inhibition of <i>Helicobacter pylori</i> Aminoacyl-tRNA Amidotransferase by Puromycin Analogues
Bibliographic record
Abstract
Recent genomic studies revealed the absence of glutaminyl-tRNA synthetase and/or asparaginyl-tRNA synthetase in many bacteria and archaea. The survival of microorganisms missing one or both of these essential enzymes implies an alternative pathway for the formation of Gln-tRNA Gln and Asn-tRNA Asn . This indirect pathway involves misacylation of tRNA Gln with Glu (or tRNA Asn with Asp) by a nondiscriminating synthetase and subsequent transamidation of the misacylated aa-tRNA by an amidotransferase. Analogues of the natural product puromycin have been developed to inhibit this class of enzymes which has been only recently investigated at the mechanistic and structural levels. The widespread use of the indirect transamidation pathway among prominent human pathogens and its absence in the cytosol of mammalian cells identify aminoacyl-tRNA amidotransferases as an interesting target for the development of antimicrobial agents with a novel mode of action. These mechanism-based inhibitors will provide useful probes for further mechanistic investigations and ligands for X-ray crystallography.
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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 | 0.000 | 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) | 0.001 | 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 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".