Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine
- Author(s)
- Wong, W; Bai, XC; Brown, A; Fernandez, IS; Hanssen, E; Condron, M; Tan, YH; Baum, J; Scheres, SH;
- Journal Title
- Elife
- Publication Type
- Journal Article
- 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 A 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.
- Publisher
- eLife Sciences
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.7554/eLife.03080
- Open Access at Publisher's Site
http://elifesciences.org/content/early/2014/06/09/eLife.03080/article-data- Terms of Use/Rights Notice
- This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Creation Date: 2014-06-12 07:46:21