8P2F

Staphylococcus aureus 70S ribosome with elongation factor G locked with fusidic acid cyclopentane in post-translocational state

これはPDB形式変換不可エントリーです。

8P2F の概要

• エントリーDOI: 10.2210/pdb8p2f/pdb
• EMDBエントリー: 17363
• 分子名称: 50S ribosomal protein L28, 23S ribosomal RNA, 5S ribosomal RNA, ... (61 entities in total)
• 機能のキーワード: ribosome, fusidic acid, ef-g, antibiotic
• 由来する生物種: Staphylococcus aureus subsp. aureus NCTC 8325; 詳細
• タンパク質・核酸の鎖数: 54
• 化学式量合計: 2275201.02

構造登録者

Gonzalez-Lopez, A.,Selmer, M. (登録日: 2023-05-16, 公開日: 2024-05-01, 最終更新日: 2025-03-12)

主引用文献

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

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: 38902339
DOI: 10.1038/s41598-024-64868-x

実験手法

ELECTRON MICROSCOPY (2.44 Å)