Substrate-dependent switching of the allosteric binding mechanism of aminoglycoside (6') acetyltransferase-Ii
Bibliographic record
Abstract
Enzyme activity is commonly controlled by allostery, where ligand binding at one site alters the activities of distant sites.Classical explanations for multi-subunit proteins involve conformational transitions that are fundamentally deterministic.For example, in the MWC paradigm, conformational transitions are concerted, occurring simultaneously in all subunits.In the KNF paradigm, conformational transitions are sequential, only occurring in ligand-bound subunits.In contrast, recent models predict conformational changes that are governed by probabilities rather than absolute rules.In order to better understand allostery at the molecular level, we applied a recently-developed spectroscopic/calorimetric method to the interactions of a dimeric enzyme with two different ligands.Surprisingly, conformational transitions are concerted for one ligand and sequential for the other.This switching behaviour shows that allostery can be inherently probabilistic even when individual ligands appear to follow classical deterministic models, with MWC (concerted) versus KNF (sequential) character controlled by the relative energies of remodeling conformations and subunit interfaces.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".