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Record W4410429680 · doi:10.1021/acs.jcim.5c00462

Entabolons: How Metabolites Modify the Biochemical Function of Proteins and Cause the Correlated Behavior of Proteins in Pathways

2025· review· en· W4410429680 on OpenAlexaff
Jeffrey Skolnick, Bharath Srinivasan, Samuel Skolnick, Hongyi Zhou

Bibliographic record

VenueJournal of Chemical Information and Modeling · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrobial Metabolic Engineering and Bioproduction
Canadian institutionsInstitute of Cancer Research
FundersNational Institute of General Medical SciencesNational Institutes of Health
KeywordsFunction (biology)ChemistryComputational biologyBiologyBiochemistryCell biology

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Although there are over 100,000 distinct human metabolites, their biological significance is often not fully appreciated. Metabolites can reshape the protein pockets to which they bind by COLIG formation, thereby influencing enzyme kinetics and altering the monomer–multimer equilibrium in protein complexes. Binding a common metabolite to a set of protein monomers or multimers results in metabolic entanglements that couple the conformational states and functions of nonhomologous, nonphysically interacting proteins that bind the same metabolite. These shared metabolites might provide the collective behavior responsible for protein pathway formation. Proteins whose binding and functional behavior is modified by a set of metabolites are termed an “entabolon”─a portmanteau of metabolic entanglement and metabolon. 55%–60% (22%–24%) of pairs of nonenzymatic proteins that likely bind the same metabolite have a p -value that they are in the same pathway, which is <0.05 (0.0005). Interestingly, the most populated pairs of proteins common to multiple pathways bind ancient metabolites. Similarly, we suggest how metabolites can possibly activate, terminate, or preclude transcription and other nucleic acid functions and may facilitate or inhibit the binding of nucleic acids to proteins, thereby influencing transcription and translation processes. Consequently, metabolites likely play a critical role in the organization and function of biological systems.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.025
GPT teacher head0.262
Teacher spread0.237 · 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 designTheoretical or conceptual
Domainnot available
GenreReview

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

Citations3
Published2025
Admission routes1
Has abstractyes

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