Adenine Aminohydrolase from Leishmania donovani
Bibliographic record
Abstract
Background: Purine salvage in Leishmania is an indispensable nutritional process.Results: Adenine aminohydrolase, a key purine enzyme in Leishmania, has been characterized biochemically and genetically.Conclusion: Adenine aminohydrolase is a unique enzyme in purine salvage that converts 6-aminopurines into 6-oxypurines.Significance: Functional characterization of key enzymes is crucial for understanding purine salvage and ultimately for targeting the pathway with drugs. Adenine aminohydrolase (AAH) is an enzyme that is not present in mammalian cells and is found exclusively inLeishmania among the protozoan parasites that infect humans.AAH plays a paramount role in purine metabolism in this genus by steering 6-aminopurines into 6-oxypurines.Leishmania donovani AAH is 38 and 23% identical to Saccharomyces cerevisiae AAH and human adenosine deaminase enzymes, respectively, catalyzes adenine deamination to hypoxanthine with an apparent K m of 15.4 M, and does not recognize adenosine as a substrate.Western blot analysis established that AAH is expressed in both life cycle stages of L. donovani, whereas subcellular fractionation and immunofluorescence studies confirmed that AAH is localized to the parasite cytosol.Deletion of the AAH locus in intact parasites established that AAH is not an essential gene and that ⌬aah cells are capable of salvaging the same range of purine nucleobases and nucleosides as wild type L. donovani.The ⌬aah null mutant was able to infect murine macrophages in vitro and in mice, although the parasite loads in both model systems were modestly reduced compared with wild type infections.The ⌬aah lesion was also introduced into a conditionally lethal ⌬hgprt/⌬xprt mutant in which viability was dependent on pharmacologic ablation of AAH by 2-deoxycoformycin.The ⌬aah/ ⌬hgprt/⌬xprt triple knock-out no longer required 2-deoxycoformycin for growth and was avirulent in mice with no persistence after a 4-week infection.These genetic studies underscore the paramount importance of AAH to purine salvage by L. donovani.
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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 | 0.001 |
| 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".