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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2qn2]] 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=2QN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QN2 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2qn2]] 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=2QN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QN2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MA:MASLINIC+ACID'>0MA</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]] 2.698Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MA:MASLINIC+ACID'>0MA</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</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;'>[[2qn1|2qn1]]</div></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=2qn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qn2 OCA], [https://pdbe.org/2qn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qn2 RCSB], [https://www.ebi.ac.uk/pdbsum/2qn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qn2 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=2qn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qn2 OCA], [https://pdbe.org/2qn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qn2 RCSB], [https://www.ebi.ac.uk/pdbsum/2qn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qn2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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.
| + | [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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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Phosphorylase]]
| + | [[Category: Alexacou K-M]] |
| - | [[Category: Alexacou, K M]] | + | [[Category: Hayes J]] |
| - | [[Category: Hayes, J]] | + | [[Category: Leonidas DD]] |
| - | [[Category: Leonidas, D D]] | + | [[Category: Oikonomakos NG]] |
| - | [[Category: Oikonomakos, N G]] | + | [[Category: Zographos SE]] |
| - | [[Category: Zographos, S E]] | + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Glycogenolysis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[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
Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) or no activity ( 21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb-asiatic acid and GPb-maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition.
Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies.,Wen X, Sun H, Liu J, Cheng K, Zhang P, Zhang L, Hao J, Zhang L, Ni P, Zographos SE, Leonidas DD, Alexacou KM, Gimisis T, Hayes JM, Oikonomakos NG J Med Chem. 2008 Jun 26;51(12):3540-54. Epub 2008 Jun 3. PMID:18517260[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wen X, Sun H, Liu J, Cheng K, Zhang P, Zhang L, Hao J, Zhang L, Ni P, Zographos SE, Leonidas DD, Alexacou KM, Gimisis T, Hayes JM, Oikonomakos NG. Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies. J Med Chem. 2008 Jun 26;51(12):3540-54. Epub 2008 Jun 3. PMID:18517260 doi:10.1021/jm8000949
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