{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ghose DA"],"funding":["Howard Hughes Medical Institute","NIGMS NIH HHS"],"pagination":["4496-4507"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12739935"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(11)"],"pubmed_abstract":["Toxin-antitoxin (TA) systems are widespread antiphage defense elements in bacteria that may impede successful phage therapy. Phage-encoded inhibitors of these systems have been discovered that enhance phage infection capacity. We used fragment-based design with deep-learning scoring functions to design peptide inhibitors of the toxin RelE. Our peptides extend a fragment of the native RelB antitoxin and are sufficient to inhibit RelE toxicity. Successful inhibitors share a highly conserved binding mode that mimics the native antitoxin but have diverse sequences, with alternative contacts used to form the peptide-protein interface. Designed peptides show different interaction specificities toward RelE family proteins, distinct from the wild-type RelB antitoxin, and inhibit the antiphage defe"],"journal":["ACS synthetic biology"],"pubmed_title":["Design of Specific Peptide Inhibitors of Toxin-Antitoxin-Mediated Antiphage Defense."],"pmcid":["PMC12739935"],"funding_grant_id":["R35 GM149227"],"pubmed_authors":["Swanson SR","Ghose DA","Laub MT","Birnbaum F","Keating AE","Britton D","Gan JL","Mahoney EM"],"additional_accession":[]},"is_claimable":false,"name":"Design of Specific Peptide Inhibitors of Toxin-Antitoxin-Mediated Antiphage Defense.","description":"Toxin-antitoxin (TA) systems are widespread antiphage defense elements in bacteria that may impede successful phage therapy. Phage-encoded inhibitors of these systems have been discovered that enhance phage infection capacity. We used fragment-based design with deep-learning scoring functions to design peptide inhibitors of the toxin RelE. Our peptides extend a fragment of the native RelB antitoxin and are sufficient to inhibit RelE toxicity. Successful inhibitors share a highly conserved binding mode that mimics the native antitoxin but have diverse sequences, with alternative contacts used to form the peptide-protein interface. Designed peptides show different interaction specificities toward RelE family proteins, distinct from the wild-type RelB antitoxin, and inhibit the antiphage defe","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-06T05:56:05.226Z","creation":"2026-05-27T03:11:53.059Z"},"accession":"S-EPMC12739935","cross_references":{"pubmed":["41139285"],"doi":["10.1021/acssynbio.5c00498"]}}