Characterization of Plasmodium falciparum Holo‐ACP Synthase: a Potential Antimalarial Drug Target
Bibliographic record
Abstract
The protozoan parasite Plasmodium falciparum is responsible for the most lethal form of malaria and kills about one million people annually, most of whom are children in sub‐Saharan Africa. Fatty acid synthesis (FAS) is a validated antimalarial strategy: it occurs in a specialized parasite organelle (the apicoplast) and uses a dissociated type II FAS system similar to bacteria. Bioinformatics analysis indicates that P. falciparum encodes a single enzyme, holo‐ACP synthase ( Pf AcpS), responsible for activating acyl carrier protein (ACP) involved in FAS. Pf AcpS consists of a signal/leader peptide, a large N‐terminal domain of unknown function, and a C‐terminal domain (PfAcpS‐C) that is highly homologous (30–50% similarity) to trimeric bacterial AcpS enzymes. We have expressed and isolated the soluble Pf AcpS‐C domain and shown that it catalyzes the transfer of (acyl)phosphopantetheine to Pf ACP from coenzyme A or from its derivatives acetyl‐CoA and octanoyl CoA. Pf AcpS exhibited much lower activity than E. coli AcpS and preferred higher concentrations of CoA derivatives. Several novel inhibitors of E. coli AcpS also blocked Pf AcpS activity, although the degree of inhibition differed between the enzymes. The sequence similarity between Pf AcpS‐C and bacterial AcpS enzymes suggests that drugs targeting the latter might also inhibit P. falciparum growth and pathogenesis. (Supported by NSERC)
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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 | 0.001 |
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".