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Updated: Feb 6, 2026

Monitoring Conformational Dynamics of Single Unmodified Proteins using Plasmonic Nanotweezers
Published on: March 21, 2025
Ligand-Driven Conformational Dynamics Influences Selectivity of UbiX
Szymon Żaczek1, Justyna Kowalska1, Agnieszka Dybala-Defratyka1
1Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
Abstract:
Up until now, it has remained elusive as to why the flavin prenyltransferase UbiX requires dimethylallyl monophosphate (DMAP) as one of its cosubstrates instead of dimethylallyl pyrophosphate (DMAPP), even though the former is not used in metabolic pathways, while the latter is a common isoprenoid precursor. Herein, mainly on the basis of molecular dynamics (MD) simulations, we demonstrate that the selectivity of UbiX may be governed by its conformational dynamics. The hydrogen-bonding network of UbiX does not facilitate a proper encompassing of DMAPP. This induces significant conformational changes of the enzyme that result mostly in unreactive trajectories, whereas DMAP remains at a catalytically competent position throughout the performed simulations. Within the presented study, we provide a justification for the atypical selectivity of UbiX.
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