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Record W1985934608 · doi:10.1074/jbc.m112.412809

Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus

2012· article· en· W1985934608 on OpenAlexafffund
Danielle D. Visschedyk, Amanda Rochon, W. Tempel, Svetoslav Dimov, Hee‐Won Park, A. Rod Merrill

Bibliographic record

VenueJournal of Biological Chemistry · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBacillus and Francisella bacterial research
Canadian institutionsUniversity of TorontoStructural Genomics ConsortiumUniversity of Guelph
FundersNational Research Council CanadaCanadian Institutes of Health ResearchStiftelsen för Strategisk ForskningOntario Genomics InstituteKarolinska InstitutetCystic Fibrosis CanadaWestern Economic Diversification CanadaWellcome TrustOntario GenomicsGenome CanadaUniversity of SaskatchewanNatural Sciences and Engineering Research Council of CanadaKnut och Alice Wallenbergs StiftelseCanadian Light SourceOntario Innovation TrustGlaxoSmithKline
KeywordsBacillus anthracisAnthrax toxinBacillus cereusMicrobiologyCereusBiologyVirulence factorToxinPore-forming toxinAnthrax vaccinesNAD+ kinaseMolecular biologyEnzymeBiochemistryVirulenceRecombinant DNABacteriaMicrobial toxinsGeneGenetics

Abstract

fetched live from OpenAlex

We identified Certhrax, the first anthrax-like mART toxin from the pathogenic G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with anthrax lethal factor from Bacillus anthracis; however, we have shown that the toxicity of Certhrax resides in the mART domain, whereas anthrax uses a metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to require protective antigen for host cell entry. This two-domain enzyme was shown to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax localizes to distinct regions within mouse RAW264.7 cells by 10 min postinfection and is extranuclear in its cellular location. Substitution of catalytic residues shows that the mART function is responsible for the toxicity, and it binds NAD(+) with high affinity (K(D) = 52.3 ± 12.2 μM). We report the 2.2 Å Certhrax structure, highlighting its structural similarities and differences with anthrax lethal factor. We also determined the crystal structures of two good inhibitors (P6 (K(D) = 1.7 ± 0.2 μM, K(i) = 1.8 ± 0.4 μM) and PJ34 (K(D) = 5.8 ± 2.6 μM, K(i) = 9.6 ± 0.3 μM)) in complex with Certhrax. As with other toxins in this family, the phosphate-nicotinamide loop moves toward the NAD(+) binding site with bound inhibitor. These results indicate that Certhrax may be important in the pathogenesis of B. cereus.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.030
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.027
GPT teacher head0.277
Teacher spread0.250 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations38
Published2012
Admission routes2
Has abstractyes

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