Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites
Bibliographic record
Abstract
Transition metal chemistry is essential to life, where metal binding to DNA, RNA, and proteins underpins all facets of the central dogma of biology. In this context, metals in proteins are typically studied as static active site cofactors. However, the emergence of transition metal signaling, where mobile metal pools can transiently bind to biological targets beyond active sites, is expanding this conventional view of bioinorganic chemistry. This Minireview focuses on the concept of metalloallostery, using copper as a canonical example of how metals can regulate protein function by binding to remote allosteric sites (e.g., exosites). We summarize advances in and prospects for the field, including imaging dynamic transition metal signaling pools, allosteric inhibition or activation of protein targets by metal binding, and metal-dependent signaling pathways that underlie nutrient vulnerabilities in diseases spanning obesity, fatty liver disease, cancer, and neurodegeneration.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 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".