Post‐translational modification of matrix metalloproteinase‐2 by peroxynitrite
Bibliographic record
Abstract
Matrix metalloproteinases (MMPs) are key enzymes in the development and remodeling of tissues. Disruption of the interaction between a conserved Cys residue in the propeptide domain and Zn 2+ in the catalytic site activates MMPs. Enhanced biosynthesis of peroxynitrite (ONOO‾) is implicated in heart failure and myocardial ischemia/reperfusion (I/R) injury, where activated MMP‐2 was shown to degrade important intracellular targets, e.g. troponin I (TnI), myosin light chain‐1 and α‐actinin. We investigated the mechanisms by which ONOO‾ may activate full length 72 kDa MMP‐2 in vitro. Challenging MMP‐2 with ONOO‾ resulted in a biphasic change in MMP‐2 activity, with low μM ONOO‾ increasing and high μM reducing its activity. Changes in the V max of the enzyme and no significant effect on the K M were observed using a synthetic fluorogenic substrate. Addition of glutathione (GSH) did not potentiate the effect of ONOO‾, but prevented the loss of MMP‐2 activity induced by higher concentrations of ONOO‾. Mass spectrometry analysis of the reaction of ONOO‾ with either MMP‐2 or synthetic peptide KPRCGNPDVANYNFFPR identified several structural modifications, including sulfhydryl oxidation and, in the presence of GSH, reversible glutathiolation of the critical Cys. These data suggest that ONOO‾ can modify the critical Cys of the propeptide domain in MMP‐2 and that may be responsible for its activation in the heart.
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 | 0.000 | 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 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".