8QMU
The complex of Glycogen Phosphorylase with (-)-Epigallocatechin-3-gallate (EGCG).
Summary for 8QMU
| Entry DOI | 10.2210/pdb8qmu/pdb |
| Descriptor | 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) |
| Functional Keywords | transferase, inhibitor, glycogen phosphorylase, epigallocatechin-3- gallate |
| Biological source | Oryctolagus cuniculus (rabbit) |
| Total number of polymer chains | 1 |
| Total formula weight | 98453.27 |
| Authors | Alexopoulos, S.,Papakostopoulou, S.,Koulas, M.S.,Leonidas, D.D.,Skamnaki, V. (deposition date: 2023-09-25, release date: 2024-10-30, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 39433280DOI: 10.1021/acs.jafc.4c06920 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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