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Updated: Feb 5, 2026

Crystallization and Structural Determination of an Enzyme:Substrate Complex by Serial Crystallography in a Versatile Microfluidic Chip
Published on: March 20, 2021
Crystal structure of GSK3β in complex with the flavonoid, morin
Kuglae Kim1, Jeong Seok Cha2, Jin-Sik Kim3
1Department 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.
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.
Insights
Morin, a natural flavonoid, inhibits GSK3β by binding to its ATP pocket, reducing Alzheimer
Area of Science:
- Biochemistry
- Neuroscience
- Structural Biology
Background:
- Glycogen synthase kinase 3 beta (GSK3β) is a key kinase in cellular signaling.
- GSK3β hyperphosphorylates tau proteins, a hallmark of Alzheimer's disease (AD).
- Morin, a natural flavonoid, is a known GSK3β inhibitor with therapeutic potential for AD.
Purpose of the Study:
- To determine the crystal structure of GSK3β in complex with morin.
- To elucidate the inhibitory mechanism of morin on GSK3β.
- To explore morin's potential as a functional food and therapeutic scaffold for AD.
Main Methods:
- X-ray crystallography
- Biochemical assays
- Structural analysis
Main Results:
- The crystal structure of GSK3β in complex with morin was determined.
- Morin inhibits GSK3β by binding to the ATP binding pocket.
- This binding interaction provides a structural basis for morin's inhibitory activity.
Conclusions:
- Morin's inhibition of GSK3β offers a potential strategy for preventing AD.
- The determined structure provides insights for developing novel therapeutics based on the morin scaffold.
- Morin shows promise as a functional food ingredient for AD prevention.
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