9G1Z

Structure of Candida albicans 80S ribosome in complex with mefloquine (non-rotated state)

これはPDB形式変換不可エントリーです。

9G1Z の概要

• エントリーDOI: 10.2210/pdb9g1z/pdb
• 関連するPDBエントリー: 8CQ7 8CQW 8CRE 8OEQ
• EMDBエントリー: 50957
• 分子名称: 60S ribosomal protein L20, 18S rRNA, 40S ribosomal protein S0, ... (82 entities in total)
• 機能のキーワード: candida albicans, ribosome, readthrough, mefloquine
• 由来する生物種: Candida albicans SC5314; 詳細
• タンパク質・核酸の鎖数: 79
• 化学式量合計: 3115602.29

構造登録者

Kolosova, O.,Zgadzay, Y.,Stetsenko, A.,Atamas, A.,Jenner, L.B.,Guskov, A.,Yusupov, M. (登録日: 2024-07-10, 公開日: 2025-04-23, 最終更新日: 2025-05-07)

主引用文献

Kolosova, O.,Zgadzay, Y.,Stetsenko, A.,Sukhinina, A.P.,Atamas, A.,Validov, S.,Rogachev, A.,Usachev, K.,Jenner, L.,Dmitriev, S.E.,Yusupova, G.,Guskov, A.,Yusupov, M.
Mechanism of read-through enhancement by aminoglycosides and mefloquine.
Proc.Natl.Acad.Sci.USA, 122:e2420261122-e2420261122, 2025

PubMed Abstract: Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle cryo-EM, we obtained structures of the eukaryotic ribosome in complexes with several aminoglycosides (geneticin G418, paromomycin, and hygromycin B) and the antimalarial drug mefloquine (MFQ), which has also been identified as a read-through enhancer. Our study reveals a binding site of MFQ, which holds significant promise for the development of therapies targeting premature termination codon-related genetic and oncological diseases. The results underscore the crucial role of the bridge B7b/c in mediating the effects of MFQ on subunit rotation dynamics. Through a comprehensive analysis of the interactions between the drugs and the eukaryotic ribosome, we propose a unifying hypothesis for read-through enhancement by small molecules, highlighting the role of decoding center rearrangements and intersubunit rotation dynamics.

PubMed: 40273100
DOI: 10.1073/pnas.2420261122

実験手法

ELECTRON MICROSCOPY (3.1 Å)