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Evidence for a Catalytic Strategy to Promote Nucleophile Activation in Metal-Dependent RNA-Cleaving Ribozymes and 8-17 DNAzyme.

ABSTRACT: An unique catalytic strategy was recently reported for the glmS ribozyme [Bingaman et al., Nat. Chem. Biol.2017, 13, 439-445] that involves promotion of productive hydrogen bonding of the O2' nucleophile to facilitate its activation. We provide broad evidence of this strategy in the hammerhead, pistol, and VS ribozymes and 8-17 DNAzyme, enabled by a functionally important divalent metal ion that interacts with the scissile phosphate and disrupts nonproductive competitive hydrogen bonding with the O2' nucleophile. This strategy, designated tertiary gamma (3°?) catalysis, illustrates an additional role for divalent ions in ribozyme catalysis.

SUBMITTER: Ganguly A

PROVIDER: S-EPMC6902279 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Evidence for a Catalytic Strategy to Promote Nucleophile Activation in Metal-Dependent RNA-Cleaving Ribozymes and 8-17 DNAzyme.

Ganguly Abir A Weissman Benjamin P BP Piccirilli Joseph A JA York Darrin M DM

ACS catalysis 20191027 12

An unique catalytic strategy was recently reported for the <i>glm</i>S ribozyme [Bingaman et al., Nat. Chem. Biol.2017, 13, 439-445] that involves promotion of productive hydrogen bonding of the O2' nucleophile to facilitate its activation. We provide broad evidence of this strategy in the hammerhead, pistol, and VS ribozymes and 8-17 DNAzyme, enabled by a functionally important divalent metal ion that interacts with the scissile phosphate and disrupts nonproductive competitive hydrogen bonding ...[more]

PMID: 31840007

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