Kinetics of the inhibition of calmodulin-dependent protein kinase II by pea protein-derived peptides
Bibliographic record
Abstract
Calmodulin (CaM) is a ubiquitous protein present in all living cells and is involved in calcium-mediated activation of various physiologically important enzymes.Agents that bind to CaM can prevent activity of CaM-dependent protein kinase ll (CaMKll), an enzyme that has been implicaied in the initiation and propagation of chronic diseases.Agents that decrease or block the activity of CaMKll can reduce or eliminate excessive protein phosphorylation and, therefore, minimize or prevent associated pathological conditions.lnhibitors of CaM usually have either a net positive charge or a net hydrophobic character.Therefore, pea protein isolate with high levels of positively charged amino acids was enzymatically hydrolyzed to generate peptides with net positive charges.The peptides were separated on a cation-exchange column to obtain two peptide fractions that differed in level of positive charges.CaM-binding determination showed that fraction #2 had higher contents of basic amino acid residues and almost three times affinity for CaM when compared with fraction #1 .Enzyme inhibition kinetics was studied for peptides to see if they could inhibit CaMKll activity.lnhibition by the two peptide fractions followed a competitive manner and fraction #2 had a higher inhibition constant than fraction #1 .Fluorescence spectrophotometry and circular dichroism (CD) were used to determine the structural changes of CaM in the presence of enzyme and inhibitory peptides.The results showed thai interactions between CaM and inhibitory peptides led to the unfolding of CaM and exposure of previously buried hydrophobic groups.Peptide #2 was more effective than peptide #1 in causing unfolding of CaM.CD studies showed that the inhibitory peptides reduced the amount of c¿-helix siructure, a conformation that seems to be required for optimum interaction of CaM with target enzymes.Excessive unfolding of CaM by the inhibitory peptides led to increased interaction with CaMKll followed by unfolding of enzyme structure and reduction in enzyme activity.lt was concluded that pea protein-derived low molecular weight peptides with net positive charges interacted strongly and caused excessive unfolding of CaM, which reduced the ability of CaM to activate CaMKll; howeve¡ this inhibition can be removed by increasing the concentrations of CaM. ACKNOWLEGMENTFirst and foremost, I would sincerely like to
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".