4MI9
Crystal structure of Gpb in complex with SUGAR (N-[(3R)-3-(4-ETHYLPHENYL)BUTANOYL]-BETA-D-GLUCOPYRANOSYLAMINE) (S20)
Summary for 4MI9
| Entry DOI | 10.2210/pdb4mi9/pdb |
| Related | 4MHO 4MHS 4MI3 4MI6 4MIC |
| Descriptor | Glycogen phosphorylase, muscle form, N-[(3R)-3-(4-ethylphenyl)butanoyl]-beta-D-glucopyranosylamine (3 entities in total) |
| Functional Keywords | alpha and beta protein, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits) |
| Total number of polymer chains | 1 |
| Total formula weight | 95862.44 |
| Authors | Kantsadi, A.L.,Chatzileontiadou, D.S.M.,Leonidas, D.D. (deposition date: 2013-08-30, release date: 2014-07-23, Last modification date: 2023-12-06) |
| Primary citation | Parmenopoulou, V.,Kantsadi, A.L.,Tsirkone, V.G.,Chatzileontiadou, D.S.,Manta, S.,Zographos, S.E.,Molfeta, C.,Archontis, G.,Agius, L.,Hayes, J.M.,Leonidas, D.D.,Komiotis, D. Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-d-glucopyranosylamines. Bioorg.Med.Chem., 22:4810-4825, 2014 Cited by PubMed Abstract: 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-β-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 377μM while two of them were effective at causing inactivation of GP in rat hepatocytes at low μM 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. PubMed: 25092521DOI: 10.1016/j.bmc.2014.06.058 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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