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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2qrh]] 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=2QRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QRH FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2qrh]] 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=2QRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QRH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M08:(5R,7R,8S,9S,10R)-7-(HYDROXYMETHYL)-3-PHENYL-1,6-DIOXA-2-AZASPIRO[4.5]DEC-2-ENE-8,9,10-TRIOL'>M08</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]] 1.83Å</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=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=M08:(5R,7R,8S,9S,10R)-7-(HYDROXYMETHYL)-3-PHENYL-1,6-DIOXA-2-AZASPIRO[4.5]DEC-2-ENE-8,9,10-TRIOL'>M08</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;'>[[2qrg|2qrg]]</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=2qrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qrh OCA], [https://pdbe.org/2qrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qrh RCSB], [https://www.ebi.ac.uk/pdbsum/2qrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qrh 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=2qrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qrh OCA], [https://pdbe.org/2qrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qrh RCSB], [https://www.ebi.ac.uk/pdbsum/2qrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qrh 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: Chrysina ED]] |
| - | [[Category: Chrysina, E D]] | + | [[Category: Kizilis G]] |
| - | [[Category: Kizilis, G]] | + | [[Category: Leonidas DD]] |
| - | [[Category: Leonidas, D D]] | + | [[Category: Oikonomakos NG]] |
| - | [[Category: Oikonomakos, N G]] | + | [[Category: Zographos SE]] |
| - | [[Category: Zographos, S E]] | + | |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Allosteric enzyme]]
| + | |
| - | [[Category: Carbohydrate metabolism]]
| + | |
| - | [[Category: Glycogen metabolism]]
| + | |
| - | [[Category: Glycogenolysis]]
| + | |
| - | [[Category: Glycosyltransferase]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Type 2 diabetes]]
| + | |
| 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
A series of glucopyranosylidene-spiro-isoxazolines was prepared through regio- and stereoselective [3+2]-cycloaddition between the methylene acetylated exo-glucal and aromatic nitrile oxides. The deprotected cycloadducts were evaluated as inhibitors of muscle glycogen phosphorylase b. The carbohydrate-based family of five inhibitors displays K(i) values ranging from 0.63 to 92.5 microM. The X-ray structures of the enzyme-ligand complexes show that the inhibitors bind preferentially at the catalytic site of the enzyme retaining the less active T-state conformation. Docking calculations with GLIDE in extra-precision (XP) mode yielded excellent agreement with experiment, as judged by comparison of the predicted binding modes of the five ligands with the crystallographic conformations and the good correlation between the docking scores and the experimental free binding energies. Use of docking constraints on the well-defined positions of the glucopyranose moiety in the catalytic site and redocking of GLIDE-XP poses using electrostatic potential fit-determined ligand partial charges in quantum polarized ligand docking (QPLD) produced the best results in this regard.
Glucose-based spiro-isoxazolines: a new family of potent glycogen phosphorylase inhibitors.,Benltifa M, Hayes JM, Vidal S, Gueyrard D, Goekjian PG, Praly JP, Kizilis G, Tiraidis C, Alexacou KM, Chrysina ED, Zographos SE, Leonidas DD, Archontis G, Oikonomakos NG Bioorg Med Chem. 2009 Oct 15;17(20):7368-80. Epub 2009 Sep 2. PMID:19781947[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Benltifa M, Hayes JM, Vidal S, Gueyrard D, Goekjian PG, Praly JP, Kizilis G, Tiraidis C, Alexacou KM, Chrysina ED, Zographos SE, Leonidas DD, Archontis G, Oikonomakos NG. Glucose-based spiro-isoxazolines: a new family of potent glycogen phosphorylase inhibitors. Bioorg Med Chem. 2009 Oct 15;17(20):7368-80. Epub 2009 Sep 2. PMID:19781947 doi:10.1016/j.bmc.2009.08.060
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