Insights into the mechanism of the teichoic acid polymerase from Bacillus subtilis and related enzymes
Bibliographic record
Abstract
Teichoic acids (TA) are phosphate rich polymers which make up a significant proportion of the Gram‐positive bacterial cell wall. Despite their abundance, little is known regarding their function or biosynthesis. In addition, the teichoic acid biosynthetic pathway is comprised of several indispensable genes whose products represent potential targets for novel antibiotics. The TagF protein from Bacillus subtilis 168 is the poly(glycerol phosphate) polymerase responsible for the synthesis of wall TA and is the prototype member of a poorly understood family of similar enzymes. TagF shares no significant homology with any protein of known function. Alignment of its amino acid sequence with predicted TA synthetic enzymes from other organisms identified highly conserved regions specific to the TagF‐like family. Structural experiments localized the active site of TagF to its carboxyl‐terminus, consistent with bioinformatic predictions. pH analysis combined with site‐directed mutagenesis and in vivo complementation experiments identified two conserved histidine residues which are critical to TagF function. H474A and H612A variants showed a 5000‐fold reduction in k cat /K m while variants in four other conserved acidic residues showed minimal loss of activity. We extended these results to suggest mechanistic commonality across the TagF‐like family by demonstrating that analogous substitutions also impacted the activity of the homologous TagB protein. Our experiments give the first insights into how the members of this mysterious family of glycerophosphotransferases promote catalysis. This work was funded by the CIHR.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".