6AZ3

Cryo-EM structure of of the large subunit of Leishmania ribosome bound to paromomycin

This is a non-PDB format compatible entry.

Summary for 6AZ3

• Entry DOI: 10.2210/pdb6az3/pdb
• Related: 6AZ1
• EMDB information: 7024 7025
• Descriptor: ribosomal protein uL2, 60S ribosomal protein L23, putative, Probable 60S ribosomal protein L14, ... (53 entities in total)
• Functional Keywords: leishmania, ribosome, aminoglycoside, paromomycin, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Leishmania donovani; More
• Total number of polymer chains: 50
• Total formula weight: 2119489.92

Authors

Shalev-Benami, M.,Zhang, Y.,Rozenberg, H.,Nobe, Y.,Taoka, M.,Matzov, D.,Zimmerman, E.,Bashan, A.,Isobe, T.,Jaffe, C.L.,Yonath, A.,Skiniotis, G. (deposition date: 2017-09-09, release date: 2017-12-06, Last modification date: 2024-10-23)

Primary citation

Shalev-Benami, M.,Zhang, Y.,Rozenberg, H.,Nobe, Y.,Taoka, M.,Matzov, D.,Zimmerman, E.,Bashan, A.,Isobe, T.,Jaffe, C.L.,Yonath, A.,Skiniotis, G.
Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.
Nat Commun, 8:1589-1589, 2017

PubMed Abstract: Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics.

PubMed: 29150609
DOI: 10.1038/s41467-017-01664-4

Experimental method

ELECTRON MICROSCOPY (2.5 Å)