Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 4, Pages 1527-1530Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201507365
Keywords
aminoglycoside; ligand specificity; riboswitches; RNA structures; structural biology
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Funding
- Aventis Foundation
- Center for Biomolecular Magnetic Resonance (BMRZ) at the Goethe-University Frankfurt
- Deutsche Forschungsgemeinschaft [WO901/2-1, SU402/4-1]
- Deutsche Forschungsgemeinschaft (Collaborative Research Center) [(SFB) 902]
- Federal Government of Germany
- State of Thuringia
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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.
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