Activation of the glmS Ribozyme Nucleophile via Overdetermined Hydrogen Bonding

Jamie L. Bingaman, Inanllely Y. Gonzalez, Bo Wang, Philip C. Bevilacqua

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

RNA enzymes, or ribozymes, catalyze internal phosphodiester bond cleavage using diverse catalytic strategies. These include the four classic strategies: in-line nucleophilic attack, deprotonation of the 2′-OH nucleophile, protonation of the 5′-O leaving group, and stabilization of developing charge on the nonbridging oxygen atoms of the scissile phosphate. In addition, we recently identified two additional ribozyme strategies: acidification of the 2′-OH and release of the 2′-OH from inhibitory interactions. Herein, we report inverse thio effects in the presence of glmS ribozyme variants and a 1-deoxyglucosamine 6-phosphate cofactor analogue and demonstrate that activation of the 2′-OH nucleophile is promoted by competitive hydrogen bonding among diverse ribozyme moieties for the pro-RP nonbridging oxygen. We conclude that the glmS ribozyme uses an overdetermined set of competing hydrogen bond donors in its active site to ensure potent activation and regulation by the cofactor. Nucleophile activation through competitive, overdetermined hydrogen bonding could be a general strategy for ribozyme activation and may be applicable for controlling the function of ribozymes and riboswitches in the laboratory.

Original languageEnglish (US)
Pages (from-to)4313-4317
Number of pages5
JournalBiochemistry
Volume56
Issue number33
DOIs
StatePublished - Aug 22 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry

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