Cobalt as a Cofactor for α-Galactosaminidase-Catalyzed Cleavage of Blood Group Antigens
Bibliographic record
Abstract
Enzymatic cleavage of the terminal α- N -acetylgalactosamine of the A-antigen of red blood cells by gut commensal organisms such as Flavonifractor plautii is achieved in a two-step process in which a specific deacetylase initially generates a terminal galactosamine residue, and then a second α-galactosaminidase cleaves the sugar to leave the H-antigen of O blood types. An interesting question concerns how such an enzyme avoids the electrostatic destabilization of the transition state that would be imposed by the protonated amine, leading us to a structural analysis. The three-dimensional structure of this GH36 enzyme, in conjunction with mechanistic studies, reveals that, while the enzyme adopts a very similar overall structure and double displacement mechanism to those of other members of glycoside hydrolase Clan-D, the active site now contains an essential cobalt ion, which coordinates the 2-position amine of the substrate. Moreover, two other metals (zinc and manganese) appear to play structural roles, while no other Clan-D glycosidases are known to show any metal dependence. Indeed, no other glycosidase is known for such a diverse metal ion binding requirement. Coordination of the substrate amine to cobalt will suppress its protonation at the operating pH of the enzyme, thereby bypassing the problem of electrostatic destabilization of the oxocarbenium ion-like transition state and allowing the reaction to proceed efficiently. This is an alternative solution to a mechanistic problem while maintaining an otherwise very similar active site.
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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) | 0.001 | 0.001 |
| 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) | 0.001 | 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".