Mechanism of Action of OXA‐58 β‐Lactamase
Bibliographic record
Abstract
Carbapenems such as imipenem and meropenem are β‐lactam antibiotics with a wide spectrum of activity, initially designed to overcome β‐lactam resistance due to their stability toward most β‐lactamases. However, as a result of selective pressure these carbapenems have succumbed to the hydrolytic power of β‐lactamases. These enzymes hydrolyze the β‐lactam bond of these antibiotics. They are classified in four classes based on their primary sequences, classes A, B, C and D. Classes A, C and D are serine‐active site β‐lactamases and class B β‐lactamases are metallo‐enzymes. The progressively increasing ability of all four classes of β‐lactamases to hydrolyze carbapenems has been documented. Among them, Carbapenem‐hydrolyzing Class D β‐lactamases (CHDLs) are directly associated with outbreaks of carbapenem‐resistant Acinetobacter baumannii around the world and have emerged as a major problem in treatment of multidrug resistant A. baumannii , for which carbapenems have been the drug of choice. We have undertaken a structural study using H/D exchange and a kinetic study using a number of OXA‐58 mutants to delineate the mechanism of hydrolysis of imipenem by OXA‐58. Our studies show that OXA‐58 employs enzyme dynamics to gain specificity toward imipenem hydrolysis.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".