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Record W4283273802 · doi:10.1021/acs.biochem.2c00197

Sequence Divergence in the Arginase Domain of Ornithine Decarboxylase/Arginase in <i>Fusobacteriacea</i> Leads to Loss of Function in Oral Associated Species

2022· article· en· W4283273802 on OpenAlexafffund
Robert G. Mothersole, Maxim Kolesnikov, Anson Chan, Emmanuella Oduro, M.E.P. Murphy, Kirsten R. Wolthers

Bibliographic record

VenueBiochemistry · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAmino Acid Enzymes and Metabolism
Canadian institutionsOkanagan University CollegeUniversity of British Columbia, Okanagan CampusUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsArginaseOrnithineBiochemistryArginineOrnithine decarboxylaseAmino acidBiologyOrnithine decarboxylase antizymeAsparagineChemistryEnzyme

Abstract

fetched live from OpenAlex

A number of species within the Fusobacteriaceae family of Gram-negative bacteria uniquely encode for an ornithine decarboxylase/arginase (ODA) that ostensibly channels l -ornithine generated by hydrolysis of l -arginine to putrescine formation. However, two aspartate residues required for coordination to a catalytically obligatory manganese cluster of arginases are substituted for a serine and an asparagine. Curiously, these natural substitutions occur only in a clade of Fusobacterium species that inhabit the oral cavity. Herein, we expressed and isolated full-length ODA from the opportunistic oral pathogen Fusobacterium nucleatum along with the individual arginase and ornithine decarboxylase components. The crystal structure of the arginase domain reveals that it adopts the classical α/β arginase-fold, but metal ions are absent in the active site. As expected, the ureohydrolase activity with l -arginine was not detected for wild-type ODA or the isolated arginase domain. However, engineering of the complete metal coordination environment through site-directed mutagenesis restored Mn 2+ binding capacity and arginase activity, although the catalytic efficiency for l -arginine was low (60–100 M –1 s –1 ). Full-length ODA and the isolated ODC component were able to decarboxylate both l -ornithine and l -arginine to form putrescine and agmatine, respectively, but k cat / K M of l -ornithine was ∼20-fold higher compared to l -arginine. We discuss environmental conditions that may have led to the natural selection of an inactive arginase in the oral associated species of Fusobacterium .

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.012
GPT teacher head0.237
Teacher spread0.225 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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
Published2022
Admission routes2
Has abstractyes

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