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Structure and mechanism of a methyltransferase ribozyme.


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.

SUBMITTER: Deng J 

PROVIDER: S-EPMC9050513 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Structure and mechanism of a methyltransferase ribozyme.

Deng Jie J   Wilson Timothy J TJ   Wang Jia J   Peng Xuemei X   Li Mengxiao M   Lin Xiaowei X   Liao Wenjian W   Lilley David M J DMJ   Huang Lin L  

Nature chemical biology 20220317 5


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 s  ...[more]

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