Journal
NATURE CHEMICAL BIOLOGY
Volume 18, Issue 5, Pages 556-564Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41589-022-00982-z
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Funding
- Guangdong Science and Technology Department [2020B1212060018, 2020B1212030004]
- National Natural Science Foundation of China [32001639, 32171191]
- Cancer Research UK [A18604]
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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. A recently selected ribozyme can catalyze a site-specific methyl transfer reaction, and the crystal structure of this ribozyme reveals the specific binding site and suggests a catalytic mechanism involving proximity, orientation, and nucleobase-mediated general acid catalysis.
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 angstrom, 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.
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