8QMU

The complex of Glycogen Phosphorylase with (-)-Epigallocatechin-3-gallate (EGCG).

8QMU の概要

• エントリーDOI: 10.2210/pdb8qmu/pdb
• 分子名称: Glycogen phosphorylase, muscle form, (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: transferase, inhibitor, glycogen phosphorylase, epigallocatechin-3- gallate
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 98453.27

構造登録者

Alexopoulos, S.,Papakostopoulou, S.,Koulas, M.S.,Leonidas, D.D.,Skamnaki, V. (登録日: 2023-09-25, 公開日: 2024-10-30, 最終更新日: 2024-11-13)

主引用文献

Alexopoulos, S.,McGawley, M.,Mathews, R.,Papakostopoulou, S.,Koulas, S.,Leonidas, D.D.,Zwain, T.,Hayes, J.M.,Skamnaki, V.
Evidence for the Quercetin Binding Site of Glycogen Phosphorylase as a Target for Liver-Isoform-Selective Inhibitors against Glioblastoma: Investigation of Flavanols Epigallocatechin Gallate and Epigallocatechin.
J.Agric.Food Chem., 72:24070-24081, 2024

PubMed Abstract: Glycogen phosphorylase (GP) is the rate-determining enzyme in glycogenolysis, and its druggability has been extensively studied over the years for the development of therapeutics against type 2 diabetes (T2D) and, more recently, cancer. However, the conservation of binding sites between the liver and muscle isoforms makes the inhibitor selectivity challenging. Using a combination of kinetic, crystallographic, modeling, and cellular studies, we have probed the binding of dietary flavonoids epigallocatechin gallate (EGCG) and epigallocatechin (EGC) to GP isoforms. The structures of rmGPb-EGCG and rmGPb-EGC complexes were determined by X-ray crystallography, showing binding at the quercetin binding site (QBS) in agreement with kinetic studies that revealed both compounds as noncompetitive inhibitors of GP, with EGCG also causing a significant reduction in cell viability and migration of U87-MG glioblastoma cells. Interestingly, EGCG exhibits different binding modes to GP isoforms, revealing QBS as a promising site for GP targeting, offering new opportunities for the design of liver-selective GP inhibitors.

PubMed: 39433280
DOI: 10.1021/acs.jafc.4c06920

実験手法

X-RAY DIFFRACTION (2 Å)