1wut

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{{Seed}}
 
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[[Image:1wut.png|left|200px]]
 
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==Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes==
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The line below this paragraph, containing "STRUCTURE_1wut", creates the "Structure Box" on the page.
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<StructureSection load='1wut' size='340' side='right'caption='[[1wut]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
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<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>
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{{STRUCTURE_1wut| PDB=1wut | SCENE= }}
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<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>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/1wut_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1wut" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15987904}}, adds the Publication Abstract to the page
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*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15987904 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15987904}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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1WUT is a [[Single protein]] structure of sequence from [http://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].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15987904 15987904]
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A new allosteric site in glycogen phosphorylase b as a target for drug interactions., Oikonomakos NG, Skamnaki VT, Tsitsanou KE, Gavalas NG, Johnson LN, Structure. 2000 Jun 15;8(6):575-84. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10873856 10873856]
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The structure of glycogen phosphorylase b with an alkyldihydropyridine-dicarboxylic acid compound, a novel and potent inhibitor., Zographos SE, Oikonomakos NG, Tsitsanou KE, Leonidas DD, Chrysina ED, Skamnaki VT, Bischoff H, Goldmann S, Watson KA, Johnson LN, Structure. 1997 Nov 15;5(11):1413-25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9384557 9384557]
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Human liver glycogen phosphorylase inhibitors bind at a new allosteric site., Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ, Chem Biol. 2000 Sep;7(9):677-82. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10980448 10980448]
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A new class of glycogen phosphorylase inhibitors., Lu Z, Bohn J, Bergeron R, Deng Q, Ellsworth KP, Geissler WM, Harris G, McCann PE, McKeever B, Myers RW, Saperstein R, Willoughby CA, Yao J, Chapman K, Bioorg Med Chem Lett. 2003 Nov 17;13(22):4125-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14592521 14592521]
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[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
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[[Category: Phosphorylase]]
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[[Category: Brachvogel V]]
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[[Category: Single protein]]
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[[Category: Burger H-J]]
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[[Category: Brachvogel, V.]]
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[[Category: Defossa E]]
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[[Category: Burger, H J.]]
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[[Category: Herling AW]]
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[[Category: Defossa, E.]]
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[[Category: Kadereit D]]
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[[Category: Herling, A W.]]
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[[Category: Klabunde T]]
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[[Category: Kadereit, D.]]
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[[Category: Kosmopoulou MN]]
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[[Category: Klabunde, T.]]
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[[Category: Oikonomakos NG]]
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[[Category: Kosmopoulou, M N.]]
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[[Category: Sarubbi E]]
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[[Category: Oikonomakos, N G.]]
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[[Category: Schmoll D]]
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[[Category: Roedern, E von.]]
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[[Category: Schonafinger K]]
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[[Category: Sarubbi, E.]]
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[[Category: Wendt KU]]
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[[Category: Schmoll, D.]]
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[[Category: Von Roedern E]]
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[[Category: Schonafinger, K.]]
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[[Category: Wendt, K U.]]
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[[Category: Glycogenolysis]]
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[[Category: Type 2 diabetes]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:50:12 2008''
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Current revision

Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes

PDB ID 1wut

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