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What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin‐Sensing Riboswitch
Author(s) -
DuchardtFerner Elke,
GottsteinSchmidtke Sina R.,
Weigand Julia E.,
Ohlenschläger Oliver,
Wurm JanPhilip,
Hammann Christian,
Suess Beatrix,
Wöhnert Jens
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201507365
Subject(s) - riboswitch , neomycin , chemistry , ligand (biochemistry) , stereochemistry , folding (dsp implementation) , biophysics , rna , computational biology , biology , biochemistry , receptor , antibiotics , non coding rna , electrical engineering , gene , engineering
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.