Probing the stereochemistry of the active site of gamma-glutamyl transpeptidase using sulfur derivatives of l-glutamic acid
Bibliographic record
Abstract
Gamma-glutamyl transpeptidase (GGT) catalyses the transfer of a gamma-glutamyl moiety from a donor substrate to different acceptors, such as amino acids and water. GGT is known to display relatively low stereospecificity with respect to the alpha-stereocentre of its donor substrates. In this study we have studied its stereospecificity with respect to the stereocentre at the delta-position of different analogues of L-glutamic acid. Notably, L-methionine sulfoxide is well-recognised whereas L-methionine sulfone and L-methionine sulfoximine are not. Furthermore, when the synthetic gamma-diastereoisomers of L-methionine sulfoxide were separated and tested, it was discovered that GGT shows remarkable stereospecificity at the gamma-position, binding the S(C)S(S) diastereoisomer with a K(i) of 3.5 mM, whereas the S(C)R(S) diastereoisomer is not recognised. Finally, using a sulfoxide as a new pharmacophore for GGT, we have synthesized and tested an analogue of glutathione to obtain a very promising competitive inhibitor with a K(i) of (53 +/- 3) microM.
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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 | 0.000 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 teacher head, 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".