Pulsed Electron Paramagnetic Resonance Study of Domain Docking in Neuronal Nitric Oxide Synthase: The Calmodulin and Output State Perspective
Bibliographic record
Abstract
The binding of calmodulin (CaM) to neuronal nitric oxide synthase (nNOS) enables formation of the output state of nNOS for nitric oxide production. Essential to NOS function is the geometry and dynamics of CaM docking to the NOS oxygenase domain, but little is known about these details. In the present work, the domain docking in a CaM-bound oxygenase/FMN (oxyFMN) construct of nNOS was investigated using the relaxation-induced dipolar modulation enhancement (RIDME) technique, which is a pulsed electron paramagnetic resonance technique sensitive to the magnetic dipole interaction between the electron spins. A cysteine was introduced at position 110 of CaM, after which a nitroxide spin label was attached at the position. The RIDME study of the magnetic dipole interaction between the spin label and the ferric heme centers in the oxygenase domain of nNOS revealed that, with increasing [Ca(2+)], the concentration of nNOS·CaM complexes increases and reaches a maximum at [Ca(2+)]/[CaM] ≥ 4. The RIDME kinetics of CaM-bound nNOS represented monotonous decays without well-defined oscillations. The analysis of these kinetics based on the structural models for the open and docked states has shown that only about 15 ± 3% of the CaM-bound nNOS is in the docked state at any given time, while the remaining 85 ± 3% of the protein is in the open conformations characterized by a wide distribution of distances between the bound CaM and the oxygenase domain. The results of this investigation are consistent with a model that the Ca(2+)-CaM interaction causes CaM docking with the oxygenase domain. The low population of the docked state indicates that the CaM-controlled docking between the FMN and heme domains is highly dynamic.
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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 | 0.000 |
| 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) | 0.000 | 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".