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Record W2287036964 · doi:10.1021/acscentsci.5b00399

Potent Human α-Amylase Inhibition by the β-Defensin-like Protein Helianthamide

2016· article· en· W2287036964 on OpenAlex
Christina Tysoe, Leslie K. Williams, Robert A. Keyzers, Nham T. Nguyen, Chris A. Tarling, Jacqueline Wicki, Ethan D. Goddard‐Borger, A.H. Aguda, Suzanne Perry, Leonard J. Foster, Raymond J. Andersen, Gary D. Brayer, Stephen G. Withers

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueACS Central Science · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Hydrolysis and Bioactive Peptides
Canadian institutionsUniversity of British ColumbiaCanada's Michael Smith Genome Sciences Centre
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 HealthCanadian Institutes of Health ResearchUniversidade de São PauloU.S. Department of Energy
KeywordsDefensinAmylaseEscherichia coliBiologyBiochemistryChemistryPeptideEnzymeGene

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Selective inhibitors of human pancreatic α-amylase (HPA) are an effective means of controlling blood sugar levels in the management of diabetes. A high-throughput screen of marine natural product extracts led to the identification of a potent ( K i = 10 pM) peptidic HPA inhibitor, helianthamide, from the Caribbean sea anemone Stichodactyla helianthus. Active helianthamide was produced in Escherichia coli via secretion as a barnase fusion protein. X-ray crystallographic analysis of the complex of helianthamide with porcine pancreatic α-amylase revealed that helianthamide adopts a β-defensin fold and binds into and across the amylase active site, utilizing a contiguous YIYH inhibitory motif. Helianthamide represents the first of a novel class of glycosidase inhibitors and provides an unusual example of functional malleability of the β-defensin fold, which is rarely seen outside of its traditional role in antimicrobial peptides.

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.

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 score0.008
Threshold uncertainty score0.311

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 studies0.0000.001
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 head0.008
GPT teacher head0.230
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