title: What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin-Sensing Riboswitch.
abstract: To ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin-sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch-ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.
authors.affiliation: Institut für Molekulare Biowissenschaften and Zentrum für Biomolekulare Magnetische Resonanz (BMRZ), Goethe-Universität Frankfurt, Max-von-Laue Str. 9, 60438, Frankfurt/M, Deutschland.
authors.forename: Elke
authors.initials: E
authors.lastname: Duchardt-Ferner
authors.affiliation: Institut für Molekulare Biowissenschaften and Zentrum für Biomolekulare Magnetische Resonanz (BMRZ), Goethe-Universität Frankfurt, Max-von-Laue Str. 9, 60438, Frankfurt/M, Deutschland.
authors.forename: Sina R
authors.initials: SR
authors.lastname: Gottstein-Schmidtke
authors.affiliation: Fachbereich Biologie, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Deutschland.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Weigand
authors.affiliation: Biomolekulare NMR-Spektroskopie, Leibniz Institut für Altersforschung (Fritz-Lipmann-Institut), Beutenbergstrasse 11, 07745, Jena, Deutschland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.affiliation: Institut für Molekulare Biowissenschaften and Zentrum für Biomolekulare Magnetische Resonanz (BMRZ), Goethe-Universität Frankfurt, Max-von-Laue Str. 9, 60438, Frankfurt/M, Deutschland.
authors.forename: Jan-Philip
authors.initials: JP
authors.lastname: Wurm
authors.affiliation: Ribogenetics Biochemistry Lab, Jacobs Universität Bremen, 28759, Bremen, Deutschland.
authors.forename: Christian
authors.initials: C
authors.lastname: Hammann
authors.affiliation: Fachbereich Biologie, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Deutschland.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Suess
authors.affiliation: Institut für Molekulare Biowissenschaften and Zentrum für Biomolekulare Magnetische Resonanz (BMRZ), Goethe-Universität Frankfurt, Max-von-Laue Str. 9, 60438, Frankfurt/M, Deutschland. woehnert@bio.uni-frankfurt.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Wöhnert
mesh_terms: D017665:Hydroxyl Radical / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D009355:Neomycin / Q000032:analysis*; D058928:Riboswitch
chemical_list: D008024:Ligands; D058928:Riboswitch; D017665:Hydroxyl Radical; D009355:Neomycin
keywords: RNA structures; aminoglycoside; ligand specificity; riboswitches; structural biology