Crystal structure of histo‐aspartic protease (HAP) from <i>Plasmodium falciparum</i>
Bibliographic record
Abstract
Histo‐aspartic protease (HAP) from Plasmodium falciparum is involved in hemoglobin degradation by the parasite, and thus offers a promising target for antimalarial drug development. The crystal structures of the recombinant HAP, as apoenzyme and complexes with two inhibitors, pepstatin A and KNI‐10006, have been solved at 2.5, 3.3, and 3.0 Åresolution, respectively. In the apoenzyme crystals HAP forms a tight dimer, not seen before in any aspartic proteases, with the flaps that cover the active sites (residues 70‐83) adopting an open conformation. Unexpectedly, the active site of the apoenzyme was found to contain a zinc ion tightly bound to the two active site residues, His32 and Asp215 from one monomer, and to Glu278A from the other monomer, with the coordination resembling its counterparts in metalloproteases. The flap is closed in the structure of pepstatin A complex and Lys76, uniquely present at the tip of the flap in HAP, interacts with the inhibitor. The observed mode of binding of pepstatin A in the HAP active site disproves the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI‐10006 to HAP is very unusual compared to other members of the KNI series binding to aspartic proteases. The novel features of the active site of HAP should allow designing specific inhibitors that could be developed into antimalarial drugs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".