3J79

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

This is a non-PDB format compatible entry.

Summary for 3J79

• Entry DOI: 10.2210/pdb3j79/pdb
• Related: 3J7A
• EMDB information: 2660 2661
• Descriptor: 28S ribosomal RNA, 60S ribosomal protein eL8, 60S ribosomal protein uL13, ... (47 entities in total)
• Functional Keywords: emetine, ribosome-inhibitor complex, ribosome/inhibitor
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 45
• Total formula weight: 2135888.80

Authors

Wong, W.,Bai, X.C.,Brown, A.,Fernandez, I.S.,Hanssen, E.,Condron, M.,Tan, Y.H.,Baum, J.,Scheres, S.H.W. (deposition date: 2014-06-02, release date: 2014-07-16, Last modification date: 2024-02-21)

Primary citation

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:e03080-e03080, 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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)