Crystal structure of GSK3β in complex with the flavonoid, morin

Kuglae Kim; Jeong Seok Cha; Jin-Sik Kim; Jinsook Ahn; Nam-Chul Ha; Hyun-Soo Cho

doi:10.1016/j.bbrc.2018.08.182

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.

Authors

Kuglae Kim¹, Jeong Seok Cha², Jin-Sik Kim³, Jinsook Ahn⁴, Nam-Chul Ha⁵, Hyun-Soo Cho⁶

Affiliations

¹ Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27516, USA.
² Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
³ Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea; Unit on Structural and Chemical Biology of Membrane Proteins, Cell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Drive, Bethesda, MD 20892, USA.
⁴ Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
⁵ Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: hanc210@snu.ac.kr.
⁶ Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: hscho8@yonsei.ac.kr.

PMID: 30197003
DOI: 10.1016/j.bbrc.2018.08.182

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