6AZ1

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

6AZ1 の概要

• エントリーDOI: 10.2210/pdb6az1/pdb
• 関連するPDBエントリー: 6AZ3
• EMDBエントリー: 7024 7025
• 分子名称: Ribosomal protein s1e, ribosomal protein S8, ribosomal protein S8e, ... (41 entities in total)
• 機能のキーワード: leishmania donovani, ribosome, aminoglycoside, paromomycin, ribosome-antibiotic complex, ribosome/antibiotic
• 由来する生物種: Leishmania donovani; 詳細
• タンパク質・核酸の鎖数: 38
• 化学式量合計: 1416658.06

構造登録者

Shalev-Benami, M.,Zhang, Y.,Rozenberg, H.,Matzov, D.,Zimmerman, E.,Bashan, A.,Jaffe, C.L.,Yonath, A.,Skiniotis, G. (登録日: 2017-09-09, 公開日: 2017-12-06, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.7 Å)