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Record W4405006688 · doi:10.1101/2024.12.03.626642

Identification of novel inhibitors targeting serine acetyltransferase from <i>Neisseria gonorrhoeae</i>

2024· preprint· en· W4405006688 on OpenAlexaff
Keely E.A. Oldham, Wanting Jiao, Erica J. Prentice, Joanna Hicks

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicPeptidase Inhibition and Analysis
Canadian institutionsUniversity of Victoria
Fundersnot available
KeywordsNeisseria gonorrhoeaeHuman pathogenMicrobiologyAntimicrobialSerinePathogenBiologyAntibiotic resistanceEnzymeAntibioticsBacteriaBiochemistryGenetics

Abstract

fetched live from OpenAlex

Abstract Neisseria gonorrhoeae is an obligate human pathogen and the etiological agent of the sexually transmitted infection, gonorrhoea. The rapid emergence of extensively antimicrobial-resistant strains, including those resistant to all frontline antibiotics, has led to N. gonorrhoeae being labelled a priority pathogen by the World Health Organization, highlighting the need for new antimicrobial treatments. Given its absence in humans, targeting de novo cysteine biosynthesis has been identified as a promising avenue for developing new antimicrobials against drug-resistant bacteria. The biosynthesis of cysteine is catalyzed by two enzymes; serine acetyltransferase (SAT/CysE) which catalyzes the first step and O -acetylserine sulfhydrylase (OASS/CysK) that catalyzes the second step incorporating sulfur to form L-cysteine. CysE is reported to be essential for bacterial survival in several bacterial pathogens including N. gonorrhoeae . Here, we have conducted virtual inhibitor screening of commercially available compound libraries against SAT from N. gonorrhoeae ( Ng SAT). We have identified a hit compound with an IC 50 of 13.9 µM and analyzed its interactions with the enzyme’s active site. This provides a platform for the identification and development of novel SAT inhibitors to combat drug-resistant bacterial pathogens.

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 score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.011
GPT teacher head0.235
Teacher spread0.224 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

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