An RNA aptamer that shifts the reduction potential of metabolic cofactors.

Autor: Samuelian JS; Department of Chemistry, Saint Louis University, St. Louis, MO, USA., Gremminger TJ; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; KCAS, LLC, Shawnee, KS, USA., Song Z; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Poudyal RR; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.; Pfizer, Biomedicine Design, Cambridge, MA, USA., Li J; Department of Physics, University of Missouri, Columbia, MO, USA., Zhou Y; Department of Physics, University of Missouri, Columbia, MO, USA., Staller SA; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Laronde, Inc., Cambridge, MA, USA., Carballo JA; Department of Chemistry, Saint Louis University, St. Louis, MO, USA., Roychowdhury-Saha M; Department of Chemistry, Indiana University, Bloomington, IN, USA.; GRAIL, Menlo Park, CA, USA., Chen SJ; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Department of Physics, University of Missouri, Columbia, MO, USA.; Institute for Data Science and Informatics, University of Missouri, Columbia, MO, USA., Burke DH; Department of Biochemistry, University of Missouri, Columbia, MO, USA. burkedh@missouri.edu.; Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. burkedh@missouri.edu.; Department of Biological Engineering, University of Missouri, Columbia, MO, USA. burkedh@missouri.edu.; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA. burkedh@missouri.edu., Heng X; Department of Biochemistry, University of Missouri, Columbia, MO, USA. hengx@missouri.edu., Baum DA; Department of Chemistry, Saint Louis University, St. Louis, MO, USA. dana.baum@slu.edu.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2022 Nov; Vol. 18 (11), pp. 1263-1269. Date of Electronic Publication: 2022 Sep 12.
DOI: 10.1038/s41589-022-01121-4
Abstrakt: The discovery of ribozymes has inspired exploration of RNA's potential to serve as primordial catalysts in a hypothesized RNA world. Modern oxidoreductase enzymes employ differential binding between reduced and oxidized forms of redox cofactors to alter cofactor reduction potential and enhance the enzyme's catalytic capabilities. The utility of differential affinity has been underexplored as a chemical strategy for RNA. Here we show an RNA aptamer that preferentially binds oxidized forms of flavin over reduced forms and markedly shifts flavin reduction potential by -40 mV, similar to shifts for oxidoreductases. Nuclear magnetic resonance structural analysis revealed π-π and donor atom-π interactions between the aptamer and flavin that cause unfavorable contacts with the electron-rich reduced form, suggesting a mechanism by which the local environment of the RNA-binding pocket drives the observed shift in cofactor reduction potential. It seems likely that primordial RNAs could have used similar strategies in RNA world metabolisms.
(© 2022. The Author(s).)
Databáze: MEDLINE
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