β1,6‐<scp>GlcNAc</scp> Linkage to the Core Glycan on <scp>TIMP</scp>‐1 Affects Its Gelatinase Inhibitory Activities: Aberrantly Glycosylated <scp>TIMP</scp>‐1‐<scp>MMP2</scp> Complex Modeling Shows Weaker Interaction Compared to Bi‐antennary Glycosylated <scp>TIMP</scp>‐1
Bibliographic record
Abstract
Matrix metalloproteinases ( MMPs ) are proteolytic enzymes that can regulate the tumor microenvironment. Metalloproteinase‐1 ( TIMP ‐1) is a MMP inhibitor that plays a critical role in the invasion and migration of cancer cells. N ‐acetylglucosaminyltransferase‐V ( GnT ‐V) catalyzes the attachment of a β1,6‐ N ‐acetylglucosamine ( GlcNAc ) linkage to the core glycan, and TIMP ‐1 has identified target proteins for GnT ‐V. Recent research reveals that aberrantly glycosylated TIMP ‐1 showed a weaker inhibition on gelatinase, and that this aberrancy of glycosylation was closely related with cancer cell invasion and metastasis. However, the mechanism of action of glycan modification is not known at the molecular level. In this study, the bi‐antennary and aberrant glycan structures were determined by mass spectrometry, and a model of the glycosylated TIMP ‐1‐ MMP2 complex was constructed to study the effects of glycosylation on the inhibitory activity of TIMP ‐1. Then this model was used to examine the effects of attaching a β1,6‐ GlcNAc linkage to the core glycan on the interaction of TIMP ‐1 with MMP2 . The gelatinase inhibitory activity is decreased when additional a β1,6‐ GlcNAc moiety is linked to the core glycan on TIMP ‐1. The modeled structure of the glycosylated TIMP ‐1‐ MMP2 complex reveals how aberrant N‐linked glycan hinders the interaction of these molecules.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.010 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| 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; both teacher heads agree on what is shown here.
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".