4mhs

Crystal structure of Gpb in complex with SUGAR (N-[(2E)-3-(BIPHENYL-4-YL)PROP-2-ENOYL]-BETA-D-GLUCOPYRANOSYLAMINE

spinqualitylabelsall models 4mhs, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mhs 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: 26Q, DMS NonStd Res: LLP Related: 4mho, 4mi3, 4mi6, 4mi9, 4mic Activity: Phosphorylase, with EC number 2.4.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 N-acyl-beta-d-glucopyranosylamines putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a 'consensus scoring' approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constants' values, in vitro, ranged from 5 to 377muM while two of them were effective at causing inactivation of GP in rat hepatocytes at low muM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors. Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-d-glucopyranosylamines.,Parmenopoulou V, Kantsadi AL, Tsirkone VG, Chatzileontiadou DS, Manta S, Zographos SE, Molfeta C, Archontis G, Agius L, Hayes JM, Leonidas DD, Komiotis D Bioorg Med Chem. 2014 Sep 1;22(17):4810-25. doi: 10.1016/j.bmc.2014.06.058. Epub , 2014 Jul 16. PMID:25092521 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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