IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01664-4.html
   My bibliography  Save this article

Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin

Author

Listed:
  • Moran Shalev-Benami

    (Weizmann Institute of Science
    Stanford University School of Medicine)

  • Yan Zhang

    (Stanford University School of Medicine)

  • Haim Rozenberg

    (Weizmann Institute of Science)

  • Yuko Nobe

    (Tokyo Metropolitan University)

  • Masato Taoka

    (Tokyo Metropolitan University)

  • Donna Matzov

    (Weizmann Institute of Science)

  • Ella Zimmerman

    (Weizmann Institute of Science)

  • Anat Bashan

    (Weizmann Institute of Science)

  • Toshiaki Isobe

    (Tokyo Metropolitan University)

  • Charles L. Jaffe

    (Hebrew University-Hadassah Medical School)

  • Ada Yonath

    (Weizmann Institute of Science)

  • Georgios Skiniotis

    (Stanford University School of Medicine)

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.

Suggested Citation

  • Moran Shalev-Benami & Yan Zhang & Haim Rozenberg & Yuko Nobe & Masato Taoka & Donna Matzov & Ella Zimmerman & Anat Bashan & Toshiaki Isobe & Charles L. Jaffe & Ada Yonath & Georgios Skiniotis, 2017. "Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01664-4
    DOI: 10.1038/s41467-017-01664-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01664-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01664-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. K. Shanmugha Rajan & Hava Madmoni & Anat Bashan & Masato Taoka & Saurav Aryal & Yuko Nobe & Tirza Doniger & Beathrice Galili Kostin & Amit Blumberg & Smadar Cohen-Chalamish & Schraga Schwartz & Andre , 2023. "A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01664-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.