Second Half-Reaction of Nitric Oxide Synthase: Computational Insights into the Initial Step and Key Proposed Intermediate
Bibliographic record
Abstract
Density functional theory methods have been employed to investigate possible first steps in the second half-reaction of the mechanism of nitric oxide synthases (NOSs). In particular, reactions and complexes formed via transfer of either or both hydrogens of the substrates (NHA) -NHOH group to the Fe-bound O2 were considered. For each of these pathways, the effect of adding an extra electron from tetrahydrobiotperin (H4B) was also examined. The preferred initial pathway involves the simultaneous transfer of both hydrogens of the -NHOH group to the Fe(heme)-O2, without an additional electron, to give the Fe(heme)-HOOH species which lies only marginally higher in energy, 2.5 kcal mol(-1) or less, than the initial bound active site. An alternative mechanism in which only the -NH- proton of the -NHOH group is transferred to the Fe(heme)-O2 to give an Fe(heme)-OOH derivative is found to require only slightly more energy, approximately 2 kcal mol(-1). However, transfer of the proton back to the -NOH nitrogen occurs without a barrier at 298.15 K. Tetrahedral intermediates in which the Fe(heme)-O2 has attached at the guanidinium carbon (C(guan)) of NHA, that is, forms an Fe(heme)-O2-C(guan) link, have also been investigated. All examples of such species considered, that is, with or without hydrogen or electron transfers, lie significantly higher in energy by at least 29.0 kcal mol(-1) than the initial bound active site. Thus, it is suggested that such complexes are not mechanistically feasible. The implications of the present findings for the second half-reaction are also discussed.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".