Structural and functional differences of two toxins from the scorpion Pandinus imperator K.C. Klenk and T.C. Tenenholz contributed equally to this study. Atomic Coordinates of the 18 acceptable structures and the NMR-derived restraints used to generate them have been deposited with the Protein Data Bank (Research Collaboratory for Structural Bioinformatics, New Brunswick, NJ), under the file name: 1C49 (PDB ID).The Supplementary Material referred to in this article can be found at http://www.interscience.wiley.com/jpages/0887-3585/suppmat/index.html.
Bibliographic record
Abstract
The Pandinotoxins, PiTX-Kα and PiTX-Kβ, are members of the Charybdotoxin family of scorpion toxins that can be used to characterize K+ channels. PiTX-Kα differs from PiTX-Kβ, another peptide from Pandinus imperator, by one residue (P10E). When the two toxins are compared in a physiological assay, the affinity of PiTX-Kβ for voltage-gated, rapidly inactivating K+ channels in dorsal root ganglia (DRG) neurons is 800-fold lower than that of PiTX-Kα (Kα-IC50 = 8.0 nM versus Kβ-IC50 = 6,500 nM). To understand this difference, the three-dimensional structure of PiTX-Kβ was determined by nuclear magnetic resonance (NMR) spectroscopy and compared to that of PiTX-Kα. This comparison shows that structural differences between the two toxins occur at a residue that is critical for blocking K+ channels (K27) as well as at the site of the natural mutation (P10E). In PiTX-Kβ, the negatively charged carboxylate oxygen of E10 can approach the positive charge of K27 and presumably reduces the net positive charge in this region of the toxin. This is likely the reason why PiTX-Kβ binds K+ channels from DRG neurons with a much lower affinity than does PiTX-Kα. Proteins 2000;38:441–449. © 2000 Wiley-Liss, Inc.
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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 | 0.001 | 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 | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".