Human recombinant tyrosinase destabilization caused by the double mutation <scp>R217Q</scp>/<scp>R402Q</scp>
Bibliographic record
Abstract
Oculocutaneous albinism is an autosomal recessive inherited disorder associated with mutations in the TYR gene. A single missense change in the tyrosinase (Tyr) could result in partial or complete loss of catalytic activity. The effect of two genetic mutations in the same Tyr as the molecule is less studied. Here, we study single mutation variants, R217Q, R402Q, and a double mutant variant, R217Q/R402Q, to establish a link between alterations at the level of the atomic model of the protein and the disease phenotype. Human recombinant intra-melanosomal Tyr domains of Tyr and three mutant variants were expressed in T. ni. Larvae were purified using the combination of IMAC and SEC, and diphenolase activities were measured. The Tyr homology model was equilibrated using 100 ns molecular dynamics and analyzed using computational methods. The purified R217Q and R217Q/R402Q variants show decreased catalytic activities compared to those of the Tyr and R402Q variants. The R217Q/R402Q variant has the lowest protein activity and is significantly reduced.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.000 | 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".