Structural basis of product recognition by <i>Mycobacterium tuberculosis</i> fatty acid synthase
Bibliographic record
Abstract
Microbial iterative fatty acid synthases (FAS) are versatile multienzymes under scrutiny for their potential as anti-infectious targets and their biotechnological applications. They produce saturated fatty acids with defined chain length and release them as coenzyme A-conjugates. How they recognize appropriate acyl length to initiate the process of product release is unknown. Here, we resolved two intermediate state structures of FAS, one from each of the two organisms: bacterium Mycobacterium tuberculosis and yeast Saccharomyces cerevisiae. These structures reveal how acyl carrier protein (ACP) domain and nascent fatty acids interact with the substrate-promiscuous malonyl-palmitoyl transferase (MPT) domain that is involved in product cleavage from the enzyme. MPT adopts a transient channel necessary for the accommodation of long-chain fatty acids. This channel is formed by the transient retraction of a conserved arginine side chain involved in malonate binding. These insights uncover structural determinants that enable M. tuberculosis type I FAS to produce very long-chain fatty acids used for evading host immunity in tuberculosis (TB).
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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 | 0.000 |
| 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".