Supermetalation of the β Domain of Human Metallothionein 1a
Bibliographic record
Abstract
Metallothionein has been implicated in a number of functions, including toxic metal detoxification, as a metal chaperone and in metal ion homeostasis. In this paper, we demonstrate that the beta domain of human metallothionein 1a, well-known to bind three Zn(2+) or Cd(2+) ions with nine cysteinyl sulfurs, is also capable of binding an additional Cd(2+) ion, leading to the formation of the supermetalated Cd(4)-beta-rhMT 1a. This intermediate, either by itself or in concert with the alpha domain of human metallothionein, is a likely model for metal exchange with the apoenzyme, which is one of the key roles of metallothionein. Through electrospray ionization (ESI) mass spectrometry and circular dichroism (CD) and ultraviolet (UV) spectroscopy, we show that the addition of 4.4 molar equiv of CdSO(4) to a solution of Cd(3)-beta-rhMT 1a leads to the complete conversion to Cd(4)-beta-rhMT 1a. ESI mass spectrometry was used to determine the exact speciation of beta-rhMT 1a. While the UV absorption spectrum increased slightly, the CD spectrum of Cd(4)-beta-rhMT 1a showed significant changes with the appearance of a sharp monophasic peak at 252 nm in contrast to the derivative-shaped envelope of the Cd(3)-beta-rhMT 1a species [peak extrema at (+)262 and (-)236 nm], indicating disruption of the exciton coupling in the metal-thiolate cluster. Additionally, both direct and indirect (113)Cd nuclear magnetic resonance (NMR) spectra of the Cd(3)-beta-rhMT 1a and Cd(4)-beta-rhMT 1a species were recorded. The (113)Cd NMR spectrum of Cd(4)-beta-rhMT 1a contained four cadmium peaks in the tetrahedral thiolate region at 688.8, 650.3, 635.9, and 602.5 ppm. This represents the first report of both NMR data for isolated Cd(3)-beta-rhMT 1a and supermetalated Cd(4)-beta-rhMT 1a.
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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".