Investigation of the pKa of the Nucleophilic O2′ of the Hairpin Ribozyme

• DOI: 10.1021/acs.jpcb.1c06546
• Publication Date: 2021-10-25T22:21:24Z
• Authors: Andrew J. Veenis; Pengfei Li; Alexander V. Soud...; Sharon Hammes-Sch...; Philip C. Bevilacqua
• Keywords: Hairpin ribozyme; Phosphodiester bond; VS ribozyme

Small ribozymes cleave their RNA phosphodiester backbone by catalyzing a transphosphorylation reaction wherein specific O2′ functions as the nucleophile. While deprotonation of this alcohol through its acidification would increase nucleophilicity, little is known about pKa in small ribozymes, part because high pKa's are not readily accessible experimentally. Herein, we turn to molecular dynamics calculate nucleophilic hairpin ribozyme and study interactions within active site that may impact value. We estimate wild-type be 18.5 ± 0.8, which higher than reference compound, identify correlation between proper positioning for attack elevation pKa. find monovalent ions play role depression pKa, while exocyclic amine appears important organizing site. Overall, suggests raised ground state lowers during course owing metal ion interactions.