High-pressure room-temperature crystallography reveals catalytic lid dynamics even in the absence of ligands
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Bibliographic record
Abstract
Enzymes undergo local and large-scale conformational changes as required to execute each step in their catalytic cycle. Typically, ligand binding and establishment of all protein-ligand interactions generates new protein conformations essential to the chemical transformation. Without the ligand interactions, apo protein crystals often do not have sufficient interactions/bonds to adopt the catalytically “ready” conformation, an obstacle to structural studies when in crystallo binding is not possible. We have explored the use of pressure to perturb interactions and the energy landscape so as to induce active conformations. Using a diamond anvil cell at CHESS crystallography beamline 7B2, we subjected crystals of the metabolic enzyme phosphoenolpyruvate carboxykinase (PEPCK) containing only one of two ligands required for catalysis to pressures up to 4.5 kbar. PEPCK is a well-characterized system with a gating active site loop that must adopt a “closed” conformation for catalysis to occur. We show how high pressure measurements can reveal catalytically active conformations even when all ligands required for closure at ambient pressure and temperature are not present. We will also describe tips and tricks in using the diamond anvil cell to collect high pressure crystallographic data.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
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Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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