{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(12)"],"submitter":["Zhang T"],"pubmed_abstract":["Methicillin-resistant Staphylococcus aureus is a ubiquitous pathogen, posing a serious threat to human health worldwide. Thus, there is a high demand for antibiotics with distinct targets. Caseinolytic protease P (ClpP) is a promising target for combating staphylococcal infections; however, selectively activating S. aureus ClpP (SaClpP) rather than Homo sapiens ClpP (HsClpP) remains challenging. Herein, we rationally design and identify ZG297 by structure-based strategy. It binds and activates SaClpP instead of HsClpP. This is due to differentiated ligand binding attributed to crossed \"tyrosine/histidine\" amino acid pairs. ZG297 substantially inhibits the growth of a broad panel of S. aureus strains in vitro, outperforming the selective (R)-ZG197 agonist. ZG297 also functions as a potent a"],"journal":["Cell reports. Medicine"],"pagination":["101837"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11722091"],"repository":["biostudies-literature"],"pubmed_title":["Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents."],"pmcid":["PMC11722091"],"pubmed_authors":["Zhang T","Wang P","Li J","Wei B","Gan J","Lan L","Zhang M","Wu W","Zhou H","Yang CG","Zhao Y"],"additional_accession":[]},"is_claimable":false,"name":"Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents.","description":"Methicillin-resistant Staphylococcus aureus is a ubiquitous pathogen, posing a serious threat to human health worldwide. Thus, there is a high demand for antibiotics with distinct targets. Caseinolytic protease P (ClpP) is a promising target for combating staphylococcal infections; however, selectively activating S. aureus ClpP (SaClpP) rather than Homo sapiens ClpP (HsClpP) remains challenging. Herein, we rationally design and identify ZG297 by structure-based strategy. It binds and activates SaClpP instead of HsClpP. This is due to differentiated ligand binding attributed to crossed \"tyrosine/histidine\" amino acid pairs. ZG297 substantially inhibits the growth of a broad panel of S. aureus strains in vitro, outperforming the selective (R)-ZG197 agonist. ZG297 also functions as a potent a","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-01T06:02:43.441Z","creation":"2026-04-08T09:49:13.988Z"},"accession":"S-EPMC11722091","cross_references":{"pubmed":["39615486"],"doi":["10.1016/j.xcrm.2024.101837"]}}