Solution Structures of CaM‐iNOS and CaM‐eNOS peptide complexes: Effects of a phosphomimetic CaM mutation
Bibliographic record
Abstract
NMR spectroscopy is an efficient method for studying the dynamics and structures of protein‐protein and protein‐peptide complexes. Nitric oxide synthase (NOS) functions in key physiological processes. Calmodulin (CaM), is required to fully activate the enzyme. Studies have shown CaM to act like a switch that causes a conformational change in NOS through a process that is thought to be highly dynamic. To investigate the dynamic properties of CaM‐NOS interactions, we determined the solution structure of CaM bound to the inducible NOS (iNOS) and endothelial NOS (eNOS) CaM‐binding region peptides. In addition, we investigated the structural and functional effects of CaM phopsphorylation on NOS using a phosphomimetic Y99E CaM. Our results show that Y99E CaM significantly reduces maximal synthase activity of eNOS by 40% while having little effect on nNOS and iNOS activity. A comparative NMR study between Y99E CaM and wt‐CaM bound to the eNOS peptide was performed. This investigation provides important insights into the effects that CaM phosphorylation has upon the binding and activation of the NOS enzymes. This work was funded by the NSERC of Canada.
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".