Lysophospholipase from the human blood fluke, Schistosoma japonicum
Bibliographic record
Abstract
BACKGROUND: Given the unusual nature of the schistosome surface (a highly unusual lipid bi-layer) and the central role of the schistosome tegument in host-parasite relations, an enhanced understanding of the lipid biochemistry of the schistosome surface can be expected to provide new insights into schistosome pathogenesis and lead to new interventions. METHODS: Bioinformatics approaches including three-dimensional homology modeling, along with recombinant expression, dimensional gel electrophoresis, immunoblotting, and Southern hybridizations were employed to characterize a novel lysophospholipase gene transcript from Schistosoma japonicum. RESULTS: A transcript encoding a small form lysophospholipase from the egg stage of S. japonicum was isolated as an expressed sequence tag (EST). The deduced polypeptide included 227 amino acid residues, shared identity with lysophospholipases of Schistosoma mansoni and Rattus norvegicus, and esterase A of Pseudomonas fluorescens, appeared to belong to the abhydrolase_2 family of phospholipases and carboxylesterases, and was structurally related to the alpha/beta-hydrolases (pfam00561). The S. japonicum enzyme exhibited the GXSXG consensus active site characteristic of serine proteases, esterases, and lipases, and included the catalytic triad motif of Ser-Asp-His residues characteristic of serine hydrolases. Three-dimensional structural predictions accomplished using the coordinates of human acyl protein thioesterase and P. fluorescens esterase indicated that the putative catalytic triad formed by these three residues was located at the alpha/beta-hydrolase fold characteristic of the lipases and esterases. Soluble S. japonicum lysophospholipase was expressed in Escherichia coli as a recombinant enzyme of approximately 26kDa and employed to raise a mono-specific antiserum. Immunoblot analysis revealed a single 23-kDa band in both membrane-associated and soluble tissue fractions of adult schistosomes. Southern hybridization and bioinformatics analyses indicated the likely presence of allelic-specific polymorphisms and/or two copies of the lysophospholipase gene in the S. japonicum genome. CONCLUSIONS: A small form lysophospholipase has been characterized from the human schistosome, S. japonicum. The availability of the recombinant S. japonicum lysophospholipase should facilitate further characterization of the enzyme, including its substrate and inhibition profiles and its potential as an interventional target. Schistosome lysophospholipase may represent a new target for anti-schistosomal chemotherapy given that metrifonate, which targets the related enzyme acetylcholinesterase, is an effective and safe medicine for treatment of urinary schistosomiasis.
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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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".