Identification of a Thrombin-Binding Region in the Sixth Epidermal Growth Factor-like Repeat of Human Thrombomodulin
Bibliographic record
Abstract
The interaction of thrombin with a 28-residue peptide corresponding to the N-terminal subdomain of the sixth EGF-like repeat of human thrombomodulin plus the junction between the fifth and the sixth EGF-like domains was characterized in solution by use of NMR spectroscopy, particularly differential resonance perturbations and transferred nuclear Overhauser effects (transferred NOEs). The EGF-like thrombomodulin fragment, or hTM422-449, is conformationally flexible in the absence of thrombin. Upon addition of thrombin, differential resonance perturbations and transferred NOEs are observed for the thrombomodulin peptide, suggesting specific and rapidly reversible binding and structuring of hTM422-449 in complex with thrombin. Residue-specific analysis of the differential line broadening, resonance shifts, and transferred NOEs identified regions of hTM422-449 responding to thrombin binding as the N-terminal residues Thr422-Ile424 and residues His438-Ile447 corresponding to the central beta-hairpin, or B-loop, of the consensus EGF-like repeat. The formation of the beta-hairpin is supported by the pattern of transferred NOEs bringing the two beta-strands together and characterizing a type I beta-turn. Docking of the thrombomodulin peptide to the anion-binding exosite I of thrombin revealed structural details capturing binding contacts identified so far as essential for the thrombin-thrombomodulin interaction. Definition of specific interactions between thrombin and a minimal fragment of the sixth EGF-like domain of human TM may lead to the discovery of new peptidomimetic molecules as modulators of blood coagulation.
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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) | 0.000 | 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 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".