Regulating Transport Preferences of Fucosylated Sugars: Revealing Transport Mechanisms via Sugar Efflux Transporter A Transformation Into a “Tight‐in, Tight‐out” Mode
Bibliographic record
Abstract
Sugar transporters play a crucial role in cellular metabolism across diverse organisms, regulating essential biological processes through efficient substrate transport. Despite extensive research efforts, the structures and mechanisms of transporters responsible for sugars have remained elusive. In this study, we investigated the transport efficiency of the Escherichia coli sugar efflux transporter A (SetA) for lactose and fucosylated lactose. By employing site and combinatorial mutations, we obtained a mutant exhibiting approximately sixfold enhanced transporter efficiency for fucosylated lactose while retaining its potency for lactose transport. In this mutant, the fundamental amino acids responsible for recognizing the galactosyl moiety remained unchanged, yet the introduction of two face-to-face aromatic ring residues facilitated the enhanced recognition of the fucosyl moiety. This indicated the transformation of SetA from a universal transporter into a specific "tight-in, tight-out" transporter. Utilizing SetA-based structural modeling, we mapped and investigated mutations associated with diseases. The structural and biochemical insights from SET in this study offer a valuable investigating framework for understanding substrate specificity mechanisms of fucosylated sugar transporters and, by extension, other transporters in broader contexts.
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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 | 0.001 | 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".