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Record W4415258324 · doi:10.1021/jacs.5c08886

Conversion of a Heme-Dependent Dehydratase to a Piperazate Synthase Reveals the Role of the Heme Propionate Group in N–N Bond-Formation

2025· article· en· W4415258324 on OpenAlexafffund
M.A. Higgins, Nana Mirotadze, Xinjie Shi, Elesha R. Hoffarth, Yi‐Ling Du, Katherine S. Ryan

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPolyamine Metabolism and Applications
Canadian institutionsUniversity of British Columbia
FundersSLAC National Accelerator LaboratoryBasic Energy SciencesNational Institute of General Medical SciencesBiological and Environmental ResearchNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsOffice of ScienceNational Institutes of HealthNational Natural Science Foundation of ChinaU.S. Department of Energy
KeywordsDehydrataseHemePropionateEnzymeATP synthasePorphobilinogen synthaseBiosynthesisMutagenesis

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Enzymes that form nitrogen–nitrogen bonds are employed in natural product biosynthesis and the nitrogen cycle. Piperazate synthase forms the cyclic hydrazine l -piperazic acid from l - N 5 -OH-ornithine, using heme as a cofactor. In this work, we discover sequence-related enzyme NohD that instead reacts with l - N 5 -OH-ornithine to release ammonia, and we solve its structure to 1.4 Å resolution. We then employ structure-guided site-directed mutagenesis to endow variants of NohD with piperazate synthase activity. Crystal structures of the NohD variants reveal how the heme propionate changes conformation, positioning it upward toward the amino nitrogen, where it is likely to activate the amine for N–N bond-formation. This study highlights a key structural requirement for N–N bond-formation and sets the stage for the development of new N–N-bond-forming catalysts.

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 score0.004
Threshold uncertainty score0.166

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 head0.004
GPT teacher head0.238
Teacher spread0.234 · 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

Citations2
Published2025
Admission routes2
Has abstractyes

Explore more

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