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.
| Original language | English |
|---|---|
| Pages (from-to) | 519-524 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 504 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2018 Oct 2 |
Bibliographical note
Funding Information:We thank the staff scientists for assistance at the beamlines 5A and 1A of the Photon Factory, and the beamline 5C, 7A, and 11C of Pohang Light Source. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT ( NRF-2016R1A2B2013305 to HSC, NRF-2016R1A5A1010764 to HSC, NRF-2017M3A9F6029755 to HSC and NCH) and by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through Agriculture, Food and Rural Affairs Research Center Support Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) ( 710012-03-1-HD120 to NCH).
Publisher Copyright:
© 2018 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology