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

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Wong W, Bai XC, Brown A, Fernandez IS, Hanssen E, Condron M, Tan YH, Baum J, Scheres SH

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

Elife. 2014 Jun 9;3. doi: 10.7554/eLife.03080.

PubMed ID
24913268 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
40S ribosomal protein S3Q8IKH8Details
60S ribosomal protein L4Q8I431Details
60S ribosomal protein L3Q8IJC6Details
40S ribosomal protein S19C0H5C2Details
60S ribosomal protein L2Q8I3T9Details
60S ribosomal protein L27Q8IKM5Details
40S ribosomal protein S5, putativeQ8IBN5Details
40S ribosomal protein S21Q8IHS5Details
60S ribosomal protein L24, putativeQ8IEM3Details
60S ribosomal protein L23Q8IE82Details
60S ribosomal protein L17, putativeQ8IDI5Details
60S ribosomal protein L10, putativeQ8ILV2Details
Ubiquitin-60S ribosomal protein L40Q8ID50Details
60S ribosomal protein L30e, putativeQ8IJK8Details
60S ribosomal protein L21Q8ILK3Details
60S ribosomal protein L14, putativeQ8ILE8Details