Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.
Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.
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DOI：
10.1038/s41467-017-01664-4
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发表时间：
2017-11-17
影响因子：
16.6
通讯作者：
Skiniotis G
中科院分区：
文献类型：
--
作者：
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
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. Leishmaniasis is a parasitic disease transmitted by the bite of infected sand flies. Here the authors describe an atomic resolution cryo-EM structure of the Leishmania ribosome in complex with the recently approved drug paromomycin (PAR) and highlight conserved elements in the drug binding pocket that mediate PAR deleterious effects on the parasite.
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影响因子：
48
作者：
Kucukelbir, Alp;Sigworth, Fred J.;Tagare, Hemant D.
通讯作者：
Tagare, Hemant D.
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
通讯作者：
Cheng, Yifan
影响因子：
3.7
作者：
Maarouf, M;deKouchkovsky, Y;RobertGero, M
通讯作者：
RobertGero, M
DOI：
10.1111/j.1432-1033.1976.tb10587.x
发表时间：
1976-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
LANDO, D;COUSIN, MA;RAYNAUD, JP
通讯作者：
RAYNAUD, JP
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC