Study of 2'-macrolide phosphotransferase selectivity for different substrates
Bibliographic record
Abstract
Macrolides are antibiotics that have been in use since the late 1950s to treat a wide range of bacterial infections (e.g. upper respiratory infections, skin and soft–tissue infections, stomach ulcers and some venereal diseases). The structure of these antibiotics contains a lactone ring of either 14, 15, or 16 members, with a variety of sugar moieties attached. Resistance to this class of antibiotics may result from the reaction carried out by macrolide phosphotransferases [MPHs]. MPHs belong to the family of antibiotic kinases which catalyzes the transfer of a phosphate group from a nucleoside triphosphate to a specific hydroxyl on the antibiotic. However, unlike most antibiotic kinases, MPHs utilize GTP as the phosphate donor. Specifically, 2'-macrolide phosphotransferase type I [MPH(2')-I] transfers the gamma-phosphate from GTP to the 2'-hydroxyl of 14- and 15-membered ring macrolides. Crystal structure of the ternary complexes of MPH(2')-I with both 14- and 15-membered lactone macrolides have been determined. To study the basis of substrate selectivity, we have generated mutations of several amino acid residues in the macrolide-binding pocket and examined the catalytic activities of these mutants on the different classes of macrolides, including those containing a 16-membered lactone. Furthermore, we will present kinetic studies of MPH(2')-I containing mutations in the nucleoside-binding pocket in order to study the mechanism for the enzyme's preference for GTP.
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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 | 0.001 |
| 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".