1wut
From Proteopedia
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| - | [[Image:1wut.png|left|200px]] | ||
| - | < | + | ==Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes== |
| - | + | <StructureSection load='1wut' size='340' side='right'caption='[[1wut]], [[Resolution|resolution]] 2.26Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[1wut]] 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=1WUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WUT 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]] 2.26Å</td></tr> | |
| - | - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BN2:7-[2,6-DICHLORO-4-({[(2-CHLOROBENZOYL)AMINO]CARBONYL}AMINO)PHENOXY]HEPTANOIC+ACID'>BN2</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=1wut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wut OCA], [https://pdbe.org/1wut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wut RCSB], [https://www.ebi.ac.uk/pdbsum/1wut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wut 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. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/1wut_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wut ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acyl ureas were discovered as a novel class of inhibitors for glycogen phosphorylase, a molecular target to control hyperglycemia in type 2 diabetics. This series is exemplified by 6-{2,6-Dichloro- 4-[3-(2-chloro-benzoyl)-ureido]-phenoxy}-hexanoic acid, which inhibits human liver glycogen phosphorylase a with an IC(50) of 2.0 microM. Here we analyze four crystal structures of acyl urea derivatives in complex with rabbit muscle glycogen phosphorylase b to elucidate the mechanism of inhibition of these inhibitors. The structures were determined and refined to 2.26 Angstroms resolution and demonstrate that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Acyl ureas induce conformational changes in the vicinity of the allosteric site. Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct inhibition of AMP binding and by indirect inhibition of substrate binding through stabilization of the T' state. | ||
| - | + | Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs.,Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E Protein Sci. 2005 Jul;14(7):1760-71. PMID:15987904<ref>PMID:15987904</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 1wut" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Large Structures]] |
| - | [[ | + | |
| - | + | ||
| - | == | + | |
| - | < | + | |
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
| - | + | [[Category: Brachvogel V]] | |
| - | [[Category: Brachvogel | + | [[Category: Burger H-J]] |
| - | [[Category: Burger | + | [[Category: Defossa E]] |
| - | [[Category: Defossa | + | [[Category: Herling AW]] |
| - | [[Category: Herling | + | [[Category: Kadereit D]] |
| - | [[Category: Kadereit | + | [[Category: Klabunde T]] |
| - | [[Category: Klabunde | + | [[Category: Kosmopoulou MN]] |
| - | [[Category: Kosmopoulou | + | [[Category: Oikonomakos NG]] |
| - | [[Category: Oikonomakos | + | [[Category: Sarubbi E]] |
| - | + | [[Category: Schmoll D]] | |
| - | [[Category: Sarubbi | + | [[Category: Schonafinger K]] |
| - | [[Category: Schmoll | + | [[Category: Wendt KU]] |
| - | [[Category: Schonafinger | + | [[Category: Von Roedern E]] |
| - | [[Category: Wendt | + | |
| - | [[Category: | + | |
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Current revision
Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes
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