Structure of the Fab fragment of a humanized 5E5 antibody to a cancer-specific Tn-MUC1 epitope
Bibliographic record
Abstract
The structure of the humanized Fab from murine monoclonal antibody 5E5 specific for tumor antigen Tn-MUC1 has been determined to 1.57 Å resolution. Despite undertaking thousands of crystallization trials of the humanized 5E5 (h-5E5) Fab in the presence of either the singly or doubly glycosylated peptide antigens corresponding to Tn-MUC1, the Fab is only observed unliganded in the crystal. The conformations of the complementarity-determining regions (CDRs) of the combining site on the h-5E5 Fab do not differ significantly from those reported for liganded murine scFv at 3.0 Å resolution. While the affinity of the murine 5E5 has previously been reported as K D = 1.7 n M for the 24-mer Tn-MUC1 peptide PPAHGVT*SAPDTRPAPGS*T*APPAH prepared by in vitro glycosylation of a synthetic 24-mer MUC1 peptide, the K D of the h-5E5 Fab for the shorter doubly glycosylated glycopeptide antigens PAPGS*T*AP and APGS*T*AP was measured here as only 41 and 61 µ M , respectively. Interestingly, the single Fab molecule in the asymmetric unit of space group C 2 is observed packed head-to-head with a symmetry-related Fab across a crystallographic twofold axis such that a polypeptide loop from the light chain of each Fab is observed to insert into the antigen-binding pocket of the symmetry-related Fab. While this might suggest that binding of the Tn-MUC1 peptides may have been inhibited by a homophilic association, none was detected. The humanization process has imposed changes in the framework regions of the Fv which may have affected the Vh–Vl interface.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".