Structural mechanisms for cold‐adapted activity of phosphoenolpyruvate carboxykinase
Bibliographic record
Abstract
Abstract Temperature is a critical factor in enzyme function, as most enzymes are thermally activated. Across Earth's diverse environments (−20 to 120°C), enzymes have evolved to function optimally at their organism's growth temperature. Thermophilic enzymes must resist denaturation, while psychrophilic enzymes must maintain activity with limited thermal energy. Although principles underlying thermostability are well established, the mechanisms governing kinetic adaptation to temperature remain less understood. To investigate this, we characterized the kinetics and determined a comprehensive series of X‐ray crystal structures of a psychrophilic, GTP‐dependent phosphoenolpyruvate carboxykinase (PEPCK) bound to substrates and non‐reactive mimics of the reaction coordinate. These structures were compared to those of a mesophilic PEPCK. PEPCK is a dynamic enzyme requiring substantial conformational changes during catalysis, particularly ordering of the active site Ω‐loop lid. The psychrophilic enzyme exhibited a reduced catalytic efficiency ( k cat / K M ) and lower optimal temperature ( T opt ) relative to its mesophilic counterpart. Structural comparisons revealed substitutions in the Ω‐loop that likely increase the entropic cost of loop ordering and reduce enthalpic stabilization, hindering efficient active site closure. These results provide a mechanistic basis for cold adaptation in enzyme catalysis, linking specific structural features to altered kinetic behavior. Understanding such adaptations not only advances our knowledge of enzyme evolution but also informs protein engineering efforts aimed at designing efficient biocatalysts for industrial applications operating at non‐physiological temperatures.
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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 | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".