View source for 8r52


==The complex of Glycogen Phosphorylase with epigallocatechin (EGC).==
<StructureSection load='8r52' size='340' side='right'caption='[[8r52]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8r52]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R52 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R52 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EGT:2-(3,4,5-TRIHYDROXY-PHENYL)-CHROMAN-3,5,7-TRIOL'>EGT</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8r52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r52 OCA], [https://pdbe.org/8r52 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r52 RCSB], [https://www.ebi.ac.uk/pdbsum/8r52 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r52 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PYGM_RABIT PYGM_RABIT] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
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== Publication Abstract from PubMed ==
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.

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.,Alexopoulos S, McGawley M, Mathews R, Papakostopoulou S, Koulas S, Leonidas DD, Zwain T, Hayes JM, Skamnaki V J Agric Food Chem. 2024 Oct 21. doi: 10.1021/acs.jafc.4c06920. PMID:39433280<ref>PMID:39433280</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8r52" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Alexopoulos S]]
[[Category: Koulas MS]]
[[Category: Leonidas DD]]
[[Category: Papakostopoulou S]]
[[Category: Skamnaki V]]