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Record W4400956492 · doi:10.1021/acscentsci.4c00015

Structural Basis for Methine Excision by a Heme Oxygenase-like Enzyme

2024· article· en· W4400956492 on OpenAlexfundno aff
William C. Simke, Morgan E. Walker, Logan A Calderone, Andrew T. Putz, Jon B. Patteson, Caitlin N. Vitro, Cynthia Zizola, Matthew R. Redinbo, Maria‐Eirini Pandelia, Tyler L. Grove, Бо Ли

Bibliographic record

VenueACS Central Science · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHeme Oxygenase-1 and Carbon Monoxide
Canadian institutionsnot available
FundersDivision of Graduate EducationNational Institute of General Medical SciencesUniversity of Illinois at Urbana-ChampaignSearle Scholars ProgramNational Institutes of HealthUniversity of MaineBrandeis UniversityMcGill UniversityNational Institute of Child Health and Human DevelopmentDavid and Lucile Packard FoundationEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUniversity of North Carolina at Chapel HillNational Science Foundation
KeywordsHeme oxygenaseHemeOxygenaseChemistryEnzymeBiochemistry

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide H eme oxygenase-like d omain-containing o xidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen Pseudomonas aeruginosa, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes.

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 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 score0.106
Threshold uncertainty score0.559

Codex and Gemma teacher scores by category

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.011
GPT teacher head0.272
Teacher spread0.261 · 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.

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

Citations10
Published2024
Admission routes1
Has abstractyes

Explore more

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