Abstract
The enzyme model, mouse acetylcholinesterase, which exhibits its active site at the bottom of a narrow gorge, was investigated in the presence of different concentrations of sucrose to shed light on the protein and water dynamics in cholinesterases. The study was conducted by incoherent neutron scattering, giving access to molecular dynamics within the time scale of sub-nano to nanoseconds, in comparison with molecular dynamics simulations. With increasing sucrose concentration, we found non-linear effects, e.g., first a decrease in the dynamics at 5 wt% followed by a gain at 10 wt% sucrose. Direct comparisons with simulations permitted us to understand the following findings: at 5 wt%, sugar molecules interact with the protein surface through water molecules and damp the motions to reduce the overall protein mobility, although the motions inside the gorge are enhanced due to water depletion. When going to 10 wt% of sucrose, some water molecules at the protein surface are replaced by sugar molecules. By penetrating the protein surface, they disrupt some of the intra-protein contacts, and induce new ones, creating new pathways for correlated motions, and therefore, increasing the dynamics. This exhaustive study allowed for an explanation of the detail interactions leading to the observed non-linear behavior.
Highlights
Investigations of the impact of osmotic stress on biological systems can play major role in the case of extreme environments, for instance, high salinity in oceans, the Dead Sea, and salty lakes
The result found for the EISF of our samples points towards the same direction, as it increases at high Q values with increasing concentration of sucrose, meaning that less particles participate to the motions resolved by the instrument IN6 in the presence of the sugar the radius of confinement is almost constant
We intended to investigate the dynamics of the enzyme mouse acetylcholinesterase (mAChE) around its narrow gorge and of the water molecules, which move quickly into and out of the gorge
Summary
Investigations of the impact of osmotic stress on biological systems can play major role in the case of extreme environments, for instance, high salinity in oceans, the Dead Sea, and salty lakes. Osmotic pressure can serve as a tool to study particular parts of proteins, if access to pores or other confined regions is not possible otherwise. Such a strategy was chosen in the present case to shed light on the dynamics of the gorge of mouse acetylcholinesterase (mAChE). Due to the interest of cholinesterases as biopharmaceuticals for pre- and post-exposure treatments of organophosphorus poisoning [1], it is important to investigate the effect of sucrose as a protein structure protectant on the molecular dynamics of a model cholinesterase
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