Kinetics of Zinc and Cadmium Exchanges between Metallothionein and Carbonic Anhydrase
Bibliographic record
Abstract
The flexible coordination stoichiometry of a relatively high number of metal ions is a property unique to the metallothionein (MT) family of proteins. Mammalian MTs, for example, accommodate up to seven divalent metal ions in tetrahedral coordination geometries, using its complement of 20 cysteine ligands. The lability of the metals from these metalloclusters has been used to support the proposal of MTs acting as metal chaperones, by donating to other metal-binding proteins. The metal exchange kinetics between human MT1A and carbonic anhydrase (CA) were examined using time-dependent electrospray ionization mass spectrometry (ESI-MS). The time dependence of three different reaction conditions were studied: (i) zinc donation from partially metalated zinc-MT to apoCA; (ii) metal exchange between zinc saturated MTs and cadmium saturated CA (Cd-CA); and (iii) metal exchange between partially metalated zinc-MTs and Cd-CA. The results show that zinc donation from Zn-MTs to apo-zinc-dependent enzymes is dependent on the metal loading of the Znn-MT (where n = 1-7) and that this is a direct consequence of the increasing metal affinity for smaller values of n. Partially metalated MTs are also shown to extract cadmium from Cd-CA with significantly faster rates than metal saturated MTs and that even under zinc limiting conditions, mammalian Cd-CA would not coexist with MT. On the basis of these and previously published results, we suggest that protein-protein interactions between MT and CA facilitate metal transfers through favorable electrostatic interactions and hypothesize that the metal could be transferred between the MT and the enzyme active site using nearby metal-binding functionalities along the transfer pathway.
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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".