8P2G
Staphylococcus aureus 70S ribosome with elongation factor G locked with fusidic acid cyclopentane with a tRNA in pe/E chimeric state
This is a non-PDB format compatible entry.
Summary for 8P2G
| Entry DOI | 10.2210/pdb8p2g/pdb |
| EMDB information | 17364 |
| Descriptor | 23S ribosomal RNA, 50S ribosomal protein L13, 50S ribosomal protein L14, ... (60 entities in total) |
| Functional Keywords | ribosome, fusidic acid, ef-g, antibiotic |
| Biological source | Staphylococcus aureus subsp. aureus NCTC 8325 More |
| Total number of polymer chains | 53 |
| Total formula weight | 2251232.94 |
| Authors | Gonzalez-Lopez, A.,Selmer, M. (deposition date: 2023-05-16, release date: 2024-05-01, Last modification date: 2025-03-12) |
| Primary citation | Gonzalez-Lopez, A.,Larsson, D.S.D.,Koripella, R.K.,Cain, B.N.,Chavez, M.G.,Hergenrother, P.J.,Sanyal, S.,Selmer, M. Structures of the Staphylococcus aureus ribosome inhibited by fusidic acid and fusidic acid cyclopentane. Sci Rep, 14:14253-14253, 2024 Cited by PubMed 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 Å resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 Å 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. PubMed: 38902339DOI: 10.1038/s41598-024-64868-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.02 Å) |
Structure validation
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