2qll: Difference between revisions
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== | ==Human liver glycogen phosphorylase- GL complex== | ||
<StructureSection load='2qll' size='340' side='right'caption='[[2qll]], [[Resolution|resolution]] 2.56Å' scene=''> | |||
[[Category: | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2qll]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QLL FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fa9|1fa9]], [[1fc0|1fc0]]</div></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PYGL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </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=2qll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qll OCA], [https://pdbe.org/2qll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qll RCSB], [https://www.ebi.ac.uk/pdbsum/2qll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qll ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[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> | |||
== Function == | |||
[[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. | |||
== 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/ql/2qll_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2qll ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Disrupting the interaction between glycogen phosphorylase and the glycogen targeting subunit (G(L)) of protein phosphatase 1 is emerging as a novel target for the treatment of type 2 diabetes. To elucidate the molecular basis of binding, we have determined the crystal structure of liver phosphorylase bound to a G(L)-derived peptide. The structure reveals the C terminus of G(L) binding in a hydrophobically collapsed conformation to the allosteric regulator-binding site at the phosphorylase dimer interface. G(L) mimics interactions that are otherwise employed by the activator AMP. Functional studies show that G(L) binds tighter than AMP and confirm that the C-terminal Tyr-Tyr motif is the major determinant for G(L) binding potency. Our study validates the G(L)-phosphorylase interface as a novel target for small molecule interaction. | |||
Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase.,Pautsch A, Stadler N, Wissdorf O, Langkopf E, Moreth W, Streicher R J Biol Chem. 2008 Apr 4;283(14):8913-8. Epub 2008 Jan 15. PMID:18198182<ref>PMID:18198182</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2qll" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
[[Category: Pautsch, A]] | |||
[[Category: Pautsch, A | [[Category: Stadler, N]] | ||
[[Category: Stadler, N | [[Category: Streicher, R]] | ||
[[Category: Streicher, R | [[Category: Wissdorf, O]] | ||
[[Category: Wissdorf, O | [[Category: Allosteric enzyme]] | ||
[[Category: Carbohydrate metabolism]] | |||
[[Category: Disease mutation]] | |||
[[Category: | [[Category: Drug discovery]] | ||
[[Category: | [[Category: Glycogen metabolism]] | ||
[[Category: | [[Category: Glycogen storage disease]] | ||
[[Category: | [[Category: Glycosyltransferase]] | ||
[[Category: | [[Category: Nucleotide-binding]] | ||
[[Category: | [[Category: Phosphorylation]] | ||
[[Category: | [[Category: Protein-protein interaction]] | ||
[[Category: | [[Category: Pyridoxal phosphate]] | ||
[[Category: | [[Category: Transferase]] | ||
[[Category: | |||
[[Category: | |||
[[Category: | |||
