The Father, Son and Cholix Toxin: The Third Member of the DT Group Mono-ADP-Ribosyltransferase Toxin Family
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Bibliographic record
Abstract
The cholix toxin gene (chxA) was first identified in V. cholerae strains in 2007, and the protein was identified by bioinformatics analysis in 2008. It was identified as the third member of the diphtheria toxin group of mono-ADP-ribosyltransferase toxins along with P. aeruginosa exotoxin A and C. diphtheriae diphtheria toxin. Our group determined the structure of the full-length, three-domain cholix toxin at 2.1 Å and its C-terminal catalytic domain (cholixc) at 1.25 Å resolution. We showed that cholix toxin is specific for elongation factor 2 (diphthamide residue), similar to exotoxin A and diphtheria toxin. Cholix toxin possesses molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm and inhibition of protein synthesis. More recently, we also solved the structure of full-length cholix toxin in complex with NAD+ and proposed a new kinetic model for cholix enzyme activity. In addition, we have taken a computational approach that revealed some important properties of the NAD+-binding pocket at the residue level, including the role of crystallographic water molecules in the NAD+ substrate interaction. We developed a pharmacophore model of cholix toxin, which revealed a cationic feature in the side chain of cholix toxin active-site inhibitors that may determine the active pose. Notably, several recent reports have been published on the role of cholix toxin as a major virulence factor in V. cholerae (non-O1/O139 strains). Additionally, FitzGerald and coworkers prepared an immunotoxin constructed from domains II and III as a cancer treatment strategy to complement successful immunotoxins derived from P. aeruginosa exotoxin A.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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 it