Crystal structure of GSK3 beta in complex with the flavonoid, morin

GSK3 beta is a key kinase that plays a role in cellular signaling pathways. In Alzheimer's disease (AD), GSK3 beta has been implicated in hyperphosphorylation of tau proteins in the neuron, which is a hallmark of AD. Morin, a flavonoid that is abundant in nature, was found as an inhibitor of GSK3 beta that can reduce tau pathology in vivo and in vitro. In this study, we determined the crystal structure of GSK3 beta in complex with morin. The structure revealed that morin inhibits GSK3 beta by binding to the ATP binding pocket. Our findings augment the potential of morin as a functional food to help prevent AD, as well as to provide structural information to develop new therapeutics based on the morin skeleton. (C) 2018 Elsevier Inc. All rights reserved.