6OKK

Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit

6OKK の概要

• エントリーDOI: 10.2210/pdb6okk/pdb
• EMDBエントリー: 2660
• 分子名称: 18S ribosomal RNA, 40S ribosomal protein S7, 40S ribosomal protein S15A, ... (36 entities in total)
• 機能のキーワード: protein synthesis, antimalarial drug, ribosome, ribosome-inhibitor complex, ribosome/inhibitor
• 由来する生物種: Plasmodium falciparum (isolate 3D7); 詳細
• タンパク質・核酸の鎖数: 33
• 化学式量合計: 1263059.92

構造登録者

Wong, W.,Scheres, S.H.W. (登録日: 2019-04-13, 公開日: 2019-05-22, 最終更新日: 2020-01-08)

主引用文献

Wong, W.,Bai, X.C.,Brown, A.,Fernandez, I.S.,Hanssen, E.,Condron, M.,Tan, Y.H.,Baum, J.,Scheres, S.H.
Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine.
Elife, 3:-, 2014

PubMed Abstract: Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3.2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery.

PubMed: 24913268
DOI: 10.7554/eLife.03080

実験手法

ELECTRON MICROSCOPY (3.3 Å)