Crystal structure of GSK3β in complex with the flavonoid, morin

Biochem Biophys Res Commun. 2018 Oct 2;504(2):519-524. doi: 10.1016/j.bbrc.2018.08.182. Epub 2018 Sep 7.

Abstract

GSK3β is a key kinase that plays a role in cellular signaling pathways. In Alzheimer's disease (AD), GSK3β 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 GSK3β that can reduce tau pathology in vivo and in vitro. In this study, we determined the crystal structure of GSK3β in complex with morin. The structure revealed that morin inhibits GSK3β 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.

Keywords: Alzheimer's disease; Complex structure; GSK3; Morin; Natural compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Flavonoids / chemistry*
  • Glycogen Synthase Kinase 3 beta / chemistry*
  • Humans
  • Mice
  • Molecular Conformation
  • Protein Binding
  • Surface Plasmon Resonance

Substances

  • Flavonoids
  • morin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse