4mi9: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mi9]] 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=4MI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MI9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4mi9]] 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=4MI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MI9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=26W:N-[(3R)-3-(4-ETHYLPHENYL)BUTANOYL]-BETA-D-GLUCOPYRANOSYLAMINE'>26W</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> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=26W:N-[(3R)-3-(4-ETHYLPHENYL)BUTANOYL]-BETA-D-GLUCOPYRANOSYLAMINE'>26W</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=4mi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi9 OCA], [https://pdbe.org/4mi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mi9 RCSB], [https://www.ebi.ac.uk/pdbsum/4mi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mi9 ProSAT]</span></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=4mi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi9 OCA], [https://pdbe.org/4mi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mi9 RCSB], [https://www.ebi.ac.uk/pdbsum/4mi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mi9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 19:38, 20 September 2023
Crystal structure of Gpb in complex with SUGAR (N-[(3R)-3-(4-ETHYLPHENYL)BUTANOYL]-BETA-D-GLUCOPYRANOSYLAMINE) (S20)Crystal structure of Gpb in complex with SUGAR (N-[(3R)-3-(4-ETHYLPHENYL)BUTANOYL]-BETA-D-GLUCOPYRANOSYLAMINE) (S20)
Structural highlights
FunctionPYGM_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 PubMedGlycogen 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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