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Crowding Shifts the FMN Recognition Mechanism of Riboswitch Aptamer from Conformational Selection to Induced Fit
Author(s) -
Rode Ambadas B.,
Endoh Tamaki,
Sugimoto Naoki
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803052
Subject(s) - riboswitch , aptamer , flavin mononucleotide , chemistry , conformational isomerism , conformational change , ligand (biochemistry) , biophysics , stereochemistry , rna , biochemistry , flavin group , molecule , biology , gene , non coding rna , enzyme , receptor , genetics , organic chemistry
In bacteria, the binding between the riboswitch aptamer domain and ligand is regulated by environmental cues, such as low Mg 2+ in macrophages during pathogenesis to ensure spatiotemporal expression of virulence genes. Binding was investigated between the flavin mononucleotide (FMN) riboswitch aptamer and its anionic ligand in the presence of molecular crowding agent without Mg 2+ ion, which mimics pathogenic conditions. Structural, kinetic, and thermodynamic analyses under the crowding revealed more dynamic conformational rearrangements of the FMN riboswitch aptamer compared to dilute Mg 2+ ‐containing solution. It is hypothesized that under crowding conditions FMN binds through an induced fit mechanism in contrast to the conformational selection mechanism previously demonstrated in dilute Mg 2+ solution. Since these two mechanisms involve different conformational intermediates and rate constants, these findings have practical significance in areas such as drug design and RNA engineering.