1l7x

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[[Image:1l7x.png|left|200px]]
 
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{{STRUCTURE_1l7x| PDB=1l7x | SCENE= }}
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==Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700==
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<StructureSection load='1l7x' size='340' side='right'caption='[[1l7x]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1l7x]] 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=1L7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L7X 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]] 2.3&#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=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=CFF:CAFFEINE'>CFF</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=1l7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7x OCA], [https://pdbe.org/1l7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l7x RCSB], [https://www.ebi.ac.uk/pdbsum/1l7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l7x 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/l7/1l7x_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=1l7x 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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Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of glycogen to maintain serum glucose levels and is a therapeutic target for diabetes. HLGP is regulated by multiple interacting allosteric sites, each of which is a potential drug binding site. We used surface plasmon resonance (SPR) to screen for compounds that bind to the purine allosteric inhibitor site. We determined the affinities of a series of compounds and solved the crystal structures of three representative ligands with K(D) values from 17-550 microM. The crystal structures reveal that the affinities are partly determined by ligand-specific water-mediated hydrogen bonds and side chain movements. These effects could not be predicted; both crystallographic and SPR studies were required to understand the important features of binding and together provide a basis for the design of new allosteric inhibitors targeting this site.
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===Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700===
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Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase.,Ekstrom JL, Pauly TA, Carty MD, Soeller WC, Culp J, Danley DE, Hoover DJ, Treadway JL, Gibbs EM, Fletterick RJ, Day YS, Myszka DG, Rath VL Chem Biol. 2002 Aug;9(8):915-24. PMID:12204691<ref>PMID:12204691</ref>
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{{ABSTRACT_PUBMED_12204691}}
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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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==About this Structure==
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<div class="pdbe-citations 1l7x" style="background-color:#fffaf0;"></div>
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[[1l7x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L7X OCA].
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==See Also==
==See Also==
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*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
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*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:012204691</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Carty, M D.]]
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[[Category: Carty MD]]
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[[Category: Culp, J.]]
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[[Category: Culp J]]
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[[Category: Danley, D E.]]
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[[Category: Danley DE]]
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[[Category: Day, Y S.N.]]
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[[Category: Day YSN]]
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[[Category: Ekstrom, J L.]]
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[[Category: Ekstrom JL]]
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[[Category: Fletterick, R J.]]
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[[Category: Fletterick RJ]]
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[[Category: Gibbs, E M.]]
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[[Category: Gibbs EM]]
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[[Category: Hoover, D J.]]
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[[Category: Hoover DJ]]
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[[Category: Myszka, D G.]]
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[[Category: Myszka DG]]
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[[Category: Pauly, T A.]]
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[[Category: Pauly TA]]
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[[Category: Rath, V L.]]
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[[Category: Rath VL]]
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[[Category: Soeller, W C.]]
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[[Category: Soeller WC]]
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[[Category: Treadway, J L.]]
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[[Category: Treadway JL]]
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[[Category: Phosphorylase]]
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[[Category: Purine site]]
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[[Category: Transferase]]
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Current revision

Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700

PDB ID 1l7x

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