Allosteric Binding Sites of Aβ Peptides on the Acetylcholine Synthesizing Enzyme ChAT as Deduced by In Silico Molecular Modeling.

ABSTRACT: The native function of amyloid-β (Aβ) peptides is still unexplored. However, several recent reports suggest a prominent role of Aβ peptides in acetylcholine homeostasis. To clarify this role of Aβ, we have reported that Aβ peptides at physiological concentrations can directly enhance the catalytic efficiency of the key cholinergic enzyme, choline acetyltransferase (ChAT), via an allosteric interaction. In the current study, we further aimed to elucidate the underlying ChAT-Aβ interaction mechanism using in silico molecular docking and dynamics analysis. Docking analysis suggested two most probable binding clusters on ChAT for Aβ₄₀ and three for Aβ₄₂. Most importantly, the docking results were challenged with molecular dynamic studies of 100 ns long simulation in tripl

SUBMITTER: Baidya AT 

PROVIDER: S-EPMC9181666 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature