{"entity": "publication", "iuid": "3af9d90fbc974bc7a0a702085de9014d", "timestamp": "2026-08-10T23:41:49.603Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3af9d90fbc974bc7a0a702085de9014d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3af9d90fbc974bc7a0a702085de9014d"}}, "title": "Structures of the Staphylococcus aureus ribosome inhibited by fusidic acid and fusidic acid cyclopentane.", "authors": [{"family": "Gonz\u00e1lez-L\u00f3pez", "given": "Adri\u00e1n", "initials": "A"}, {"family": "Larsson", "given": "Daniel S D", "initials": "DSD"}, {"family": "Koripella", "given": "Ravi Kiran", "initials": "RK"}, {"family": "Cain", "given": "Brett N", "initials": "BN"}, {"family": "Chavez", "given": "Martin Garcia", "initials": "MG"}, {"family": "Hergenrother", "given": "Paul J", "initials": "PJ"}, {"family": "Sanyal", "given": "Suparna", "initials": "S"}, {"family": "Selmer", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2024-06-20", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "14", "issue": "1", "pages": "14253", "issn-l": "2045-2322"}, "abstract": "The antibiotic fusidic acid (FA) is used to treat Staphylococcus aureus infections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing its release from the ribosome after translocation. While FA, due to permeability issues, is only effective against gram-positive bacteria, the available structures of FA-inhibited complexes are from gram-negative model organisms. To fill this knowledge gap, we solved cryo-EM structures of the S. aureus ribosome in complex with mRNA, tRNA, EF-G and FA to 2.5 \u00c5 resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 \u00c5 resolution. With both FA variants, the majority of the ribosomal particles are observed in chimeric state and only a minor population in post-translocational state. As expected, FA binds in a pocket between domains I, II and III of EF-G and the sarcin-ricin loop of 23S rRNA. FA-CP binds in an identical position, but its cyclopentane moiety provides additional contacts to EF-G and 23S rRNA, suggesting that its improved resistance profile towards mutations in EF-G is due to higher-affinity binding. These high-resolution structures reveal new details about the S. aureus ribosome, including confirmation of many rRNA modifications, and provide an optimal starting point for future structure-based drug discovery on an important clinical drug target.", "doi": "10.1038/s41598-024-64868-x", "pmid": "38902339", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11190147"}, {"db": "pii", "key": "10.1038/s41598-024-64868-x"}], "notes": [], "created": "2024-10-08T09:35:37.331Z", "modified": "2025-10-29T15:01:08.155Z"}