9B4Z

E. coli 70S ribosome complex (N1-methylated 16S A1408 + arbekacin)

これはPDB形式変換不可エントリーです。

9B4Z の概要

• エントリーDOI: 10.2210/pdb9b4z/pdb
• EMDBエントリー: 44192
• 分子名称: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (58 entities in total)
• 機能のキーワード: aminoglycoside, a1408, resistance, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 56
• 化学式量合計: 2249966.58

構造登録者

Mattingly, J.M.,Dey, D.,Zelinskaya, N.,Dunham, C.M.,Conn, G.L. (登録日: 2024-03-21, 公開日: 2025-08-27, 最終更新日: 2025-09-10)

主引用文献

Dey, D.,Mattingly, J.M.,Zelinskaya, N.,Dunham, C.M.,Conn, G.L.
Basis for selective drug evasion of an aminoglycoside-resistance ribosomal RNA modification.
Nat Commun, 16:7992-7992, 2025

PubMed Abstract: Aminoglycosides disrupt the fidelity of bacterial protein synthesis, but their potent antibacterial activity is threatened by multiple resistance mechanisms, including methylation of their ribosomal RNA (rRNA) binding site. However, the impact of one such resistance-conferring methylation on N1 of helix 44 nucleotide A1408 (mA1408) is highly variable with some aminoglycosides retaining significant potency. Here, we examine bacterial susceptibility to diverse aminoglycosides, determine high-resolution electron cryomicroscopy structures of mA1408-modified 70S ribosome-aminoglycoside complexes, and perform molecular dynamics simulations to decipher the key determinants of such "resistance evasion." Collectively, these analyses reveal how some aminoglycosides adapt their conformation to accommodate mA1408, including the roles of specific ring substituents, balancing ligand strain and maintaining favorable interactions, as well as interactions made by additional functional groups that compensate for those disrupted by the modification. This work provides design principles that can guide future rational development of aminoglycosides refractory to resistance conferred by rRNA modifications.

PubMed: 40866347
DOI: 10.1038/s41467-025-63278-5

実験手法

ELECTRON MICROSCOPY (2.2 Å)