8IFD

Dibekacin-added human 80S ribosome

これはPDB形式変換不可エントリーです。

8IFD の概要

• エントリーDOI: 10.2210/pdb8ifd/pdb
• EMDBエントリー: 35413
• 分子名称: 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (83 entities in total)
• 機能のキーワード: ribosome
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 80
• 化学式量合計: 3825788.07

構造登録者

Tomono, J.,Asano, K.,Chiashi, T.,Tanaka, Y.,Yokoyama, T. (登録日: 2023-02-17, 公開日: 2024-02-14, 最終更新日: 2024-06-19)

主引用文献

Tomono, J.,Asano, K.,Chiashi, T.,Suzuki, M.,Igarashi, M.,Takahashi, Y.,Tanaka, Y.,Yokoyama, T.
Direct visualization of ribosomes in the cell-free system revealed the functional evolution of aminoglycoside.
J.Biochem., 175:587-598, 2024

PubMed Abstract: The rapid emergence of multi-drug-resistant bacteria has raised a serious public health concern. Therefore, new antibiotic developments have been highly desired. Here, we propose a new method to visualize antibiotic actions on translating ribosomes in the cell-free system under macromolecular crowding conditions by cryo-electron microscopy, designated as the DARC method: the Direct visualization of Antibiotic binding on Ribosomes in the Cell-free translation system. This new method allows for acquiring a more comprehensive understanding of the mode of action of antibiotics on the translation inhibition without ribosome purification. Furthermore, with the direct link to biochemical analysis at the same condition as cryo-EM observation, we revealed the evolution of 2-DOS aminoglycosides from dibekacin (DBK) to arbekacin (ABK) by acquiring the synthetic tailored anchoring motif to lead to stronger binding affinity to ribosomes. Our cryo-EM structures of DBK and ABK bound ribosomes in the cell-free environment clearly depicted a synthetic tailored γ-amino-α-hydroxybutyryl (HABA) motif formed additional interactions with the ribosome enhancing antibiotic bindings. This new approach would be valuable for understanding the function of antibiotics for more efficient drug development.

PubMed: 38227611
DOI: 10.1093/jb/mvae002

実験手法

ELECTRON MICROSCOPY (2.59 Å)