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| | <StructureSection load='3dds' size='340' side='right'caption='[[3dds]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='3dds' size='340' side='right'caption='[[3dds]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dds]] 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=3DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dds]] 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=3DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=26B:O-TERT-BUTYL-N-[(3-{[(2,4,6-TRIMETHYLPHENYL)CARBAMOYL]AMINO}NAPHTHALEN-2-YL)CARBONYL]-L-THREONINE'>26B</scene>, <scene name='pdbligand=CFF:CAFFEINE'>CFF</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=26B:O-TERT-BUTYL-N-[(3-{[(2,4,6-TRIMETHYLPHENYL)CARBAMOYL]AMINO}NAPHTHALEN-2-YL)CARBONYL]-L-THREONINE'>26B</scene>, <scene name='pdbligand=CFF:CAFFEINE'>CFF</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <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;'>[[3dd1|3dd1]], [[3ddw|3ddw]]</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=3dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dds OCA], [https://pdbe.org/3dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dds RCSB], [https://www.ebi.ac.uk/pdbsum/3dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dds ProSAT]</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=3dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dds OCA], [https://pdbe.org/3dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dds RCSB], [https://www.ebi.ac.uk/pdbsum/3dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dds ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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>
| + | [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 == | | == 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.
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphorylase]]
| + | [[Category: Nolte RT]] |
| - | [[Category: Nolte, R T]] | + | |
| - | [[Category: Allosteric enzyme]]
| + | |
| - | [[Category: Carbohydrate metabolism]]
| + | |
| - | [[Category: Diabetes]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Glycogen metabolism]]
| + | |
| - | [[Category: Glycogen phosphorylase]]
| + | |
| - | [[Category: Glycogen storage disease]]
| + | |
| - | [[Category: Glycosyltransferase]]
| + | |
| - | [[Category: Gp]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
3dds is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.8Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
PYGL_HUMAN Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.[1]
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.
Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.,Thomson SA, Banker P, Bickett DM, Boucheron JA, Carter HL, Clancy DC, Cooper JP, Dickerson SH, Garrido DM, Nolte RT, Peat AJ, Sheckler LR, Sparks SM, Tavares FX, Wang L, Wang TY, Weiel JE Bioorg Med Chem Lett. 2009 Feb 15;19(4):1177-82. Epub 2008 Dec 25. PMID:19138846[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Burwinkel B, Bakker HD, Herschkovitz E, Moses SW, Shin YS, Kilimann MW. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. 1998 Apr;62(4):785-91. PMID:9529348
- ↑ Thomson SA, Banker P, Bickett DM, Boucheron JA, Carter HL, Clancy DC, Cooper JP, Dickerson SH, Garrido DM, Nolte RT, Peat AJ, Sheckler LR, Sparks SM, Tavares FX, Wang L, Wang TY, Weiel JE. Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1177-82. Epub 2008 Dec 25. PMID:19138846 doi:10.1016/j.bmcl.2008.12.085
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