Conformational flexibility of human ribokinase captured in seven crystal structures
Bibliographic record
Abstract
d -ribose is a critical sugar substrate involved in the biosynthesis of nucleotides, amino acids, and cofactors, with its phosphorylation to ribose-5-phosphate by ribokinase (RK) constituting the initial step in its metabolism. RK is conserved across all domains of life, and its activity is significantly enhanced by monovalent metal (M + ) ions, particularly K + , although the precise mechanism of this activation remains unclear. In this study, we present several crystal structures of human RK in both unliganded and substrate-bound states, offering detailed insights into its substrate binding process, reaction mechanism, and conformational changes throughout the catalytic cycle. Notably, bound ATP exhibited significant conformational flexibility in its triphosphate moiety, a feature shared with other RK homologues, suggesting that achieving a catalytically productive triphosphate configuration plays a key role in regulating enzyme activity. We also identified a unique conformational change in the M + ion binding loop of human RK, specifically the flipping of the Gly306-Thr307 peptide plane, likely influenced by the ionic radius of the bound ion. These findings provide new insights into the RK reaction mechanism and its activation by M + ions, paving the way for future investigations into the allosteric regulation of human RK and related sugar kinase 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 | 0.000 |
| 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 | 0.000 | 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".