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TitleCryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine.
Journal, issue, pagesElife, Vol. 3, Year 2014
Publish dateJun 9, 2014
AuthorsWilson Wong / Xiao-chen Bai / Alan Brown / Israel S Fernandez / Eric Hanssen / Melanie Condron / Yan Hong Tan / Jake Baum / Sjors H W Scheres /
PubMed AbstractMalaria 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 ...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.
External linksElife / PubMed:24913268 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.4 Å
Structure data

2660

3j79

3j7a

6okk

EMDB-2660: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine
PDB-3j79: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, large subunit
PDB-3j7a: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit
PDB-6okk: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-2661:
Cryo-EM structure of the Plasmodium falciparum 80S ribosome
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-34G:
emetine / Emetine

Source
  • plasmodium falciparum (malaria parasite P. falciparum)
  • synthetic construct (others)
  • plasmodium falciparum (isolate 3d7) (eukaryote)
KeywordsRIBOSOME/INHIBITOR / emetine / RIBOSOME-INHIBITOR complex / Protein synthesis / antimalarial drug / RIBOSOME

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