Valine of the YVDD Motif of Moloney Murine Leukemia Virus Reverse Transcriptase: Role in the Fidelity of DNA Synthesis
Bibliographic record
Abstract
The YXDD motif is highly conserved in the reverse transcriptase family. The variable X residue is occupied by valine and methionine in MuLV RT and HIV-1 RT, respectively. Previous studies have shown that Tyr 222, the Y residue of the YXDD motif in MuLV RT, constitutes a major component of the fidelity center of the enzyme [Kaushik, N., Singh, K., Alluru, I., and Modak, M. J. (1999) Biochemistry 38, 2617-2627]. In this work, we present evidence that reverse transcriptases containing valine in the "X" position of the YXDD motif generally catalyze DNA synthesis with greater fidelity than those containing methionine or alanine. In the MuLV RT system, the two mutants V223M and V223A exhibited an overall reduced fidelity of DNA synthesis, specifically for RNA-templated reactions. Further analysis revealed that these mutants exhibit a higher efficiency of misinsertion on MS2 RNA than the wild-type enzyme for every mispair tested. However, unlike HIV-1 RT, the insensitivity of the wild-type MuLV RT to all four ddNTPs remained unchanged by mutation of V223 to Met or Ala. A 3D molecular model of the ternary complex of MuLV RT, template primer, and dNTP suggests that Val 223 along with its neighboring Tyr 222 stabilizes the substrate binding pocket via hydrophobic interactions with the dNTP substrate and template-primer.
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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) | 0.001 | 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".