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The structure and catalytic mechanism of a pseudoknot-containing hammerhead ribozyme

Author

Listed:
  • Xuelin Zhan

    (Nankai University
    Nankai University
    International Centre of Genetic Engineering and Biotechnology)

  • Timothy J. Wilson

    (The University of Dundee)

  • Zhenzhen Li

    (Nankai University
    Nankai University)

  • Jingjing Zhang

    (Nankai University
    Nankai University)

  • Yili Yang

    (International Centre of Genetic Engineering and Biotechnology)

  • David M. J. Lilley

    (The University of Dundee
    Nankai University)

  • Yijin Liu

    (Nankai University
    Nankai University)

Abstract

We have determined the crystal structure of a pseudoknot (PK)-containing hammerhead ribozyme that closely resembles the pistol ribozyme, with essentially identical secondary structure and connectivity. The activity is more sensitive to deletion of the G8 2’OH than to the absence of magnesium ions, indicating that the catalytic mechanism is the same as the extended hammerhead, and distinct from the pistol ribozyme. Here we show that nucleophilic attack is almost perfectly in-line, and the G8 2’OH is well positioned to act as general acid, being directed towards the O5’ leaving group, and 2.9 Å away from it. Despite the similarity in overall structure to the pistol ribozyme, the local structure close to the cleavage site differs, and the PK hammerhead retains its unique mechanistic identity and demonstrates enhanced activity over other hammerhead ribozymes under standard conditions.

Suggested Citation

  • Xuelin Zhan & Timothy J. Wilson & Zhenzhen Li & Jingjing Zhang & Yili Yang & David M. J. Lilley & Yijin Liu, 2024. "The structure and catalytic mechanism of a pseudoknot-containing hammerhead ribozyme," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50892-y
    DOI: 10.1038/s41467-024-50892-y
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    References listed on IDEAS

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    1. Monika Martick & Lucas H. Horan & Harry F. Noller & William G. Scott, 2008. "A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA," Nature, Nature, vol. 454(7206), pages 899-902, August.
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