Comparison of Kifunensine and 1-Deoxymannojirimycin Binding to Class I and II α-Mannosidases Demonstrates Different Saccharide Distortions in Inverting and Retaining Catalytic Mechanisms<sup>,</sup>
Bibliographic record
Abstract
Mannosidases are key enzymes in the eukaryotic N-glycosylation pathway. These enzymes fall into two broad classes (I and II) and are characteristically different in catalytic mechanism, sequence, and structure. Kifunensine is an alkaloid that is a strong inhibitor against class I alpha-mannosidases but is only a weak inhibitor against class II alpha-mannosidases. In this paper, the 1.80 A resolution crystal structure of kifunensine bound to Drosophila melanogaster Golgi alpha-mannosidase II (dGMII) is presented. Kifunensine adopts a (1,4)B boat conformation in the class II dGMII, which contrasts the (1)C(4) chair conformation seen in class I human endoplasmic reticulum alpha1,2 mannosidase (hERMI, PDB ). The observed conformations are higher in conformational energy than the global minimum (4)C(1) conformation, although the conformation in hERMI is closer to the minimum, as supported by an energy calculation. Differing conformations of 1-deoxymannojirimycin were also observed: a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively. Thus, these two alpha-mannosidase classes distort these inhibitors in distinct manners. This is likely indicative of the binding characteristics of the two different catalytic mechanisms of these enzymes.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| 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".