6az3

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

Loading... Status: waiting for Mol* initialization Structural highlights 6az3 is a 10 chain structure with sequence from Leishmania donovani. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: A2M, MG, OMC, OMG, OMU, PAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A504XXD2_LEIDO Publication Abstract from PubMed 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. Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.,Shalev-Benami M, Zhang Y, Rozenberg H, Nobe Y, Taoka M, Matzov D, Zimmerman E, Bashan A, Isobe T, Jaffe CL, Yonath A, Skiniotis G Nat Commun. 2017 Nov 17;8(1):1589. doi: 10.1038/s41467-017-01664-4. PMID:29150609 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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