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Record W2953175593 · doi:10.3390/toxins11060365

An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins

2019· article· en· W2953175593 on OpenAlexafffund
Miguel R. Lugo, A. Rod Merrill

Bibliographic record

VenueToxins · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicToxin Mechanisms and Immunotoxins
Canadian institutionsUniversity of Guelph
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsIn silicoTerminal (telecommunication)Sequence (biology)Group (periodic table)BiologyComputational biologyFunction (biology)ChemistryGeneticsComputer scienceGeneComputer network

Abstract

fetched live from OpenAlex

The C3-like toxins are single-domain proteins that represent a minimal mono-ADP-ribosyl transferase (mART) enzyme with a simple model scaffold for the entire cholera toxin (CT)-group. These proteins possess a single (A-domain) that modifies Rho proteins. In contrast, C2-like toxins require a binding/translocation partner (B-component) for intoxication. These are A-only toxins that contain the E-x-E motif, modify G-actin, but are two-domains with a C-domain possessing enzymatic activity. The N-domain of the C2-like toxins is unstructured, and its function is currently unknown. A sequence-structure-function comparison was performed on the N-terminal region of the mART domain of the enzymatic component of the CT toxin group in the CATCH fold (3.90.210.10). Special consideration was given to the N-domain distal segment, the α-lobe (α1–α4), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal α-lobe is to provide a suitable configuration (i) of the α2–α3 helices to feature the α3-motif that has a role in NAD+ substrate binding and possibly in the interaction with the protein target; (ii) the α3–α4 helices to provide the α3/4-loop with protein-protein interaction capability; and (iii) the α1-Ntail that features specialized motif(s) according to the toxin type (A-only or A-B toxins) exhibiting an effect on the catalytic activity via the ARTT-loop, with a role in the inter-domain stability, and with a function in the binding and/or translocation steps during the internalization process.

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)0.000
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 score0.454
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.009
GPT teacher head0.232
Teacher spread0.222 · 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

Citations6
Published2019
Admission routes2
Has abstractyes

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