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| | <StructureSection load='1lwo' size='340' side='right'caption='[[1lwo]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1lwo' size='340' side='right'caption='[[1lwo]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1lwo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LWO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lwo]] 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=1LWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LWO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHI:5-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID+[1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE'>CHI</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2Å</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=CHI:5-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID+[1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE'>CHI</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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">[[1h5u|1h5u]], [[1lwn|1lwn]]</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=1lwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lwo OCA], [https://pdbe.org/1lwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lwo RCSB], [https://www.ebi.ac.uk/pdbsum/1lwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lwo ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lwo OCA], [http://pdbe.org/1lwo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lwo RCSB], [http://www.ebi.ac.uk/pdbsum/1lwo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lwo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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. |
| | == 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: European rabbit]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphorylase]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Chrysina, E D]] | + | [[Category: Chrysina ED]] |
| - | [[Category: Kosmopoulou, M N]] | + | [[Category: Kosmopoulou MN]] |
| - | [[Category: Leonidas, D D]] | + | [[Category: Leonidas DD]] |
| - | [[Category: Oikonomakos, N G]] | + | [[Category: Oikonomakos NG]] |
| - | [[Category: Glycogen phosphorylase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: New allosteric site]]
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| - | [[Category: Transferase]]
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| - | [[Category: Type 2 diabetes]]
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| Structural highlights
Function
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.
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
CP320626 has been identified as a potent inhibitor, synergistic with glucose, of human liver glycogen phosphorylase a (LGPa), a possible target for type 2 diabetes therapy. CP320626 is also a potent inhibitor of human muscle GPa. In order to elucidate the structural basis of the mechanism of CP320626 inhibition, the structures of T state rabbit muscle GPa (MGPa) in complex with glucose and in complex with both glucose and CP320626 were determined at 2.0 A resolution, and refined to crystallographic R values of 0.179 (R(free)=0.218) and 0.207 (R(free)=0.235), respectively. CP320626 binds at the new allosteric site, some 33 A from the catalytic site, where glucose binds. The binding of CP320626 to MGPa does not promote extensive conformational changes except for small shifts of the side chain atoms of residues R60, V64, and K191. Both CP320626 and glucose promote the less active T state, while structural comparisons of MGPa-glucose-CP320626 complex with LGPa complexed with a related compound (CP403700) and a glucose analogue inhibitor indicate that the residues of the new allosteric site, conserved in the two isozymes, show no significant differences in their positions.
Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution.,Oikonomakos NG, Chrysina ED, Kosmopoulou MN, Leonidas DD Biochim Biophys Acta. 2003 Apr 11;1647(1-2):325-32. PMID:12686153[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oikonomakos NG, Chrysina ED, Kosmopoulou MN, Leonidas DD. Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):325-32. PMID:12686153
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