The long term objective is to apply the physicochemical properties that modified nucleosides contribute to nucleic acids to the design of pharmaceutical agents that inhibit translation. The research is focused on understanding the contributions of several modified nucleosides to RNA structural stability, ion binding, dynamics, folding, RNA-RNA interactions, and RNA-protein interactions. In particular, the contributions of modified nucleosides to the properties, structures, and functions of various domains from tRNA will be studied using CD, NMR, and biochemical methods. The information will be used to design inhibitors of translation.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular and Cellular Biophysics Study Section (BBCA)
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Lewis, Catherine D
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North Carolina State University Raleigh
Schools of Earth Sciences/Natur
United States
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Xiao, Xingqing; Agris, Paul F; Hall, Carol K (2015) Designing peptide sequences in flexible chain conformations to bind RNA: a search algorithm combining Monte Carlo, self-consistent mean field and concerted rotation techniques. J Chem Theory Comput 11:740-52
Harris, Kimberly A; Bobay, Benjamin G; Sarachan, Kathryn L et al. (2015) NMR-based Structural Analysis of Threonylcarbamoyl-AMP Synthase and Its Substrate Interactions. J Biol Chem 290:20032-43
Halvorsen, Ken; Agris, Paul F (2014) Cross-platform comparison of nucleic acid hybridization: toward quantitative reference standards. Anal Biochem 465:127-33
Spears, Jessica L; Xiao, Xingqing; Hall, Carol K et al. (2014) Amino acid signature enables proteins to recognize modified tRNA. Biochemistry 53:1125-33
Rodriguez-Hernandez, Annia; Spears, Jessica L; Gaston, Kirk W et al. (2013) Structural and mechanistic basis for enhanced translational efficiency by 2-thiouridine at the tRNA anticodon wobble position. J Mol Biol 425:3888-906
Harris, Kimberly A; Shekhtman, Alexander; Agris, Paul F (2013) Specific RNA-protein interactions detected with saturation transfer difference NMR. RNA Biol 10:1307-11
Vendeix, Franck A P; Murphy 4th, Frank V; Cantara, William A et al. (2012) Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism. J Mol Biol 416:467-85
Graham, William D; Barley-Maloney, Lise; Stark, Caren J et al. (2011) Functional recognition of the modified human tRNALys3(UUU) anticodon domain by HIV's nucleocapsid protein and a peptide mimic. J Mol Biol 410:698-715
Bilbille, Yann; Gustilo, Estella M; Harris, Kimberly A et al. (2011) The human mitochondrial tRNAMet: structure/function relationship of a unique modification in the decoding of unconventional codons. J Mol Biol 406:257-74
Harris, Kimberly A; Jones, Victoria; Bilbille, Yann et al. (2011) YrdC exhibits properties expected of a subunit for a tRNA threonylcarbamoyl transferase. RNA 17:1678-87

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