Structure and mechanism of a methyl transferase ribozyme

Jie Deng, Timothy J. Wilson, Jia Wang, Xuemei Peng, Mengxiao Li, Xiaowei Lin, Wenjian Liao, David M. J. Lilley (Lead / Corresponding author), Lin Huang (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)
    17 Downloads (Pure)

    Abstract

    Known ribozymes in contemporary biology perform a limited range of chemical catalysis, but in vitro selection has generated species that catalyze a broader range of chemistry; yet, there have been few structural and mechanistic studies of selected ribozymes. A ribozyme has recently been selected that can catalyze a site-specific methyl transfer reaction. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism involving a combination of proximity and orientation and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis. A selected methyltransferase ribozyme can thus use a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalyzed chemistry. [Figure not available: see fulltext.]

    Original languageEnglish
    Pages (from-to)556-564
    Number of pages9
    JournalNature Chemical Biology
    Volume18
    Early online date17 Mar 2022
    DOIs
    Publication statusPublished - May 2022

    Keywords

    • Biocatalysis
    • RNA

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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