1xoi

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(New page: 200px<br /> <applet load="1xoi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xoi, resolution 2.1&Aring;" /> '''Human Liver Glycogen...)
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[[Image:1xoi.gif|left|200px]]<br />
 
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<applet load="1xoi" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1xoi, resolution 2.1&Aring;" />
 
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'''Human Liver Glycogen Phosphorylase A complexed with Chloroindoloyl glycine amide'''<br />
 
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==Overview==
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==Human Liver Glycogen Phosphorylase A complexed with Chloroindoloyl glycine amide==
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The synthesis, in vitro, and in vivo biological characterization of a, series of achiral 5-chloroindoloyl glycine amide inhibitors of human liver, glycogen phosphorylase A are described. Improved potency over previously, reported compounds in cellular and in vivo assays was observed. The, allosteric binding site of these compounds was shown by X-ray, crystallography to be the same as that reported previously for, 5-chloroindoloyl norstatine amides.
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<StructureSection load='1xoi' size='340' side='right'caption='[[1xoi]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1xoi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XOI FirstGlance]. <br>
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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]] 2.1&#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=288:5-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID{[CYCLOPENTYL-(2-HYDROXY-ETHYL)-CARBAMOYL]-METHYL}-AMIDE'>288</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
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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=1xoi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xoi OCA], [https://pdbe.org/1xoi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xoi RCSB], [https://www.ebi.ac.uk/pdbsum/1xoi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xoi ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:[https://omim.org/entry/232700 232700]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.<ref>PMID:9529348</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] 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/xo/1xoi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1xoi ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Glycogen storage disease VI OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=232700 232700]]
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*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1XOI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NBG, PLP and 288 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XOI OCA].
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__TOC__
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</StructureSection>
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==Reference==
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5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization., Wright SW, Rath VL, Genereux PE, Hageman DL, Levy CB, McClure LD, McCoid SC, McPherson RK, Schelhorn TM, Wilder DE, Zavadoski WJ, Gibbs EM, Treadway JL, Bioorg Med Chem Lett. 2005 Jan 17;15(2):459-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15603973 15603973]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Gibbs EM]]
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[[Category: Gibbs, E.M.]]
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[[Category: Rath VL]]
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[[Category: Rath, V.L.]]
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[[Category: Treadway JL]]
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[[Category: Treadway, J.L.]]
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[[Category: Wright SW]]
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[[Category: Wright, S.W.]]
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[[Category: 288]]
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[[Category: NBG]]
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[[Category: PLP]]
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[[Category: allosteric enzyme]]
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[[Category: glycogen storage disease]]
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[[Category: glycosyltransferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:08:33 2007''
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Current revision

Human Liver Glycogen Phosphorylase A complexed with Chloroindoloyl glycine amide

PDB ID 1xoi

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