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ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

Author

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  • Huihao Zhou

    (The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA)

  • Litao Sun

    (The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA)

  • Xiang-Lei Yang

    (The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA)

  • Paul Schimmel

    (The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA)

Abstract

The crystal structure of prolyl tRNA synthetase simultaneously bound to its substrate ATP and its inhibitor halofuginone, a derivative of a compound used to treat malaria, indicates that (through interactions with ATP) halofuginone occupies both the amino acid and tRNA binding sites on the synthetase, revealing a new model for developing synthetase inhibitors.

Suggested Citation

  • Huihao Zhou & Litao Sun & Xiang-Lei Yang & Paul Schimmel, 2013. "ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase," Nature, Nature, vol. 494(7435), pages 121-124, February.
    • Handle: RePEc:nat:nature:v:494:y:2013:i:7435:d:10.1038_nature11774
    DOI: 10.1038/nature11774
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    Cited by:

    1. Debjit Khan & Iyappan Ramachandiran & Kommireddy Vasu & Arnab China & Krishnendu Khan & Fabio Cumbo & Dalia Halawani & Fulvia Terenzi & Isaac Zin & Briana Long & Gregory Costain & Susan Blaser & Amand, 2024. "Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m6A site accessibility," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Mark A. Tye & N. Connor Payne & Catrine Johansson & Kritika Singh & Sofia A. Santos & Lọla Fagbami & Akansha Pant & Kayla Sylvester & Madeline R. Luth & Sofia Marques & Malcolm Whitman & Maria M. Mota, 2022. "Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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