5lrf

Crystal structure of Glycogen Phosphorylase b in complex with KS389

spinqualitylabelsall models 5lrf, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lrf is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DMS, KS3, PLP Related: 5lre Activity: Phosphorylase, with EC number 2.4.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. Publication Abstract from PubMed 3-(C-Glucopyranosyl)-5aryl-1,2,4-triazoles with an aryl moiety larger than phenyl have been shown to have strong inhibitory potency (Ki values in the range of upper nM) for human liver glycogen phosphorylase (hlGP), a pharmacologically relevant target for diabetes type 2. In this study we investigate in a comparative manner the inhibitory effect of the above triazoles and their respective imidazoles on hlGPa. Kinetic studies show that the imidazole derivatives are 6-8 times more potent than their corresponding triazoles. We also seek to answer how the type of the aryl moiety affects the potency in hlGPa, and by determination of the crystal structure of rmGPb in complex with the triazole derivatives the structural basis of their inhibitory efficacy is also elucidated. Our studies revealed that the van der Waals interactions between the aryl moiety and residues in a hydrophobic pocket within the active site are mainly responsible for the variations in the potency of these inhibitors. van der Waals interactions govern C-beta-d-glucopyranosyl triazoles' nM inhibitory potency in human liver glycogen phosphorylase.,Kantsadi AL, Stravodimos GA, Kyriakis E, Chatzileontiadou DSM, Solovou TGA, Kun S, Bokor E, Somsak L, Leonidas DD J Struct Biol. 2017 Jul;199(1):57-67. doi: 10.1016/j.jsb.2017.05.001. Epub 2017, May 5. PMID:28483603 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycogen Phosphorylase

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