A Pseudohypervalent Sulfur Intermediate as an Oxidative Protective Mechanism in the Archaea Peroxiredoxin Enzyme ApTPx
Bibliographic record
Abstract
Peroxiredoxins (Prxs) are a ubiquitous class of enzymes that have central roles in a number of important physiological processes. Using a multiscale computational approach, we have investigated the mechanism by which the active-site cysteine (Cys50) in the typical 2-Cys Prx from Archaea (ApTPx) is oxidized by H 2 O 2 to sulfenic acid. In addition, its further oxidation to give a sulfinic acid and its possible alternate intramolecular reaction to form an experimentally proposed hypervalent sulfurane were examined. Oxidation of Cys50 by H 2 O 2 to give the sulfenic acid intermediate occurs in one step with a barrier of 82.1 kJ mol –1 . A two-step pathway is proposed with a very low barrier of 16.5 kJ mol –1 by which it can subsequently react with an adjacent histidyl (His42) to form the pseudohypervalent sulfurane. This pathway also involves an adjacent aspartyl (Asp45), which helps alternate the protonation state of His42. The sulfurane’s Cys50 S···Nδ His42 interaction was characterized using QTAIM, NCI, and NBO analyses and found to be a noncovalent interaction. Notably, this bond helps orient the Cys50 SOH moiety such that it is less susceptible to oxidation by H 2 O 2 to sulfinic acid. Significantly, sulfurane formation is energetically favored to further H 2 O 2 oxidation of Cys50 SOH to a sulfinic acid, providing a mechanism by which the active-site Cys50 is protected against overoxidation.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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 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".