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

Wilson Wong, Xiao Chen Bai, Alan Brown, Israel S. Fernandez, Eric Hanssen, Melanie Condron, Yan Hong Tan, Jake Baum, Sjors H.W. Scheres

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132 Scopus citations

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.

Original languageEnglish (US)
Article numbere03080
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - Jun 9 2014

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wong, W., Bai, X. C., Brown, A., Fernandez, I. S., Hanssen, E., Condron, M., Tan, Y. H., Baum, J., & Scheres, S. H. W. (2014). Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. eLife, 2014(3), [e03080]. https://doi.org/10.7554/eLife.03080