title: Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes.
abstract: Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution, and is studied in the context of RNA chemical etiology. It has a four-carbon threose backbone in place of the five-carbon ribose of natural nucleic acids, yet forms stable antiparallel complementary Watson-Crick homoduplexes and heteroduplexes with DNA and RNA. TNA base-pairs more favorably with RNA than with DNA but the reason is unknown. Here, we employed NMR, ITC, UV, and CD to probe the structural and dynamic properties of heteroduplexes of RNA/TNA and DNA/TNA. The results indicate that TNA templates the structure of heteroduplexes, thereby forcing an A-like helical geometry. NMR measurement of kinetic and thermodynamic parameters for individual base pair opening events reveal unexpected asymmetric "breathing" fluctuations of the DNA/TNA helix. The results suggest that DNA is unable to fully adapt to the conformational constraints of the rigid TNA backbone and that nucleic acid breathing dynamics are determined from both backbone and base contributions.
authors.affiliation: School of Molecular Sciences and the Biodesign Institute, Arizona State University, 551 E. University Dr., PSG-106, Tempe, AZ, 85287, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Anosova
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Robinson Research Building 868A, Nashville, TN, 37232, USA.
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Kowal
authors.affiliation: School of Molecular Sciences and the Biodesign Institute, Arizona State University, 551 E. University Dr., PSG-106, Tempe, AZ, 85287, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sisco
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA, 92697, USA.
authors.forename: Sujay
authors.initials: S
authors.lastname: Sau
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA, 92697, USA.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Liao
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA, 92697, USA.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bala
authors.affiliation: Department of Chemistry, Binghamton University, State University of New York, Science 2 Building 308, Binghamton, NY, 13902, USA.
authors.forename: Eriks
authors.initials: E
authors.lastname: Rozners
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Robinson Research Building 868A, Nashville, TN, 37232, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Egli
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA, 92697, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Chaput
authors.affiliation: School of Molecular Sciences and the Biodesign Institute, Arizona State University, 551 E. University Dr., PSG-106, Tempe, AZ, 85287, USA. wade.van.horn@asu.edu.
authors.forename: Wade D
authors.initials: WD
authors.lastname: Van Horn
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013780:Tetroses / Q000737:chemistry*
chemical_list: D013780:Tetroses; D012313:RNA; D004247:DNA; C073321:erythrose
keywords: DNA; RNA evolution; TNA; conformation analysis; nucleic acid dynamics