View source for 2qrp

==Glycogen Phosphorylase b in complex with (1R)-3'-(2-naphthyl)-spiro[1,5-anhydro-D-glucitol-1,5'-isoxazoline]==
<StructureSection load='2qrp' size='340' side='right' caption='[[2qrp]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qrp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QRP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=S06:(3S,5R,7R,8S,9S,10R)-7-(HYDROXYMETHYL)-3-(2-NAPHTHYL)-1,6-DIOXA-2-AZASPIRO[4.5]DECANE-8,9,10-TRIOL'>S06</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:2-LYSINE(3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHANE)'>LLP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qrm|2qrm]], [[2qrq|2qrq]]</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=2qrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qrp OCA], [http://pdbe.org/2qrp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qrp RCSB], [http://www.ebi.ac.uk/pdbsum/2qrp PDBsum]</span></td></tr>
</table>
== 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. 
== 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/qr/2qrp_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/chain_selection.php?pdb_ID=2ata ConSurf].
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== 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<ref>PMID:19781947</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2qrp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Oryctolagus cuniculus]]
[[Category: Phosphorylase]]
[[Category: Alexacou, K M]]
[[Category: Chrysina, E D]]
[[Category: Gizilis, G]]
[[Category: Leonidas, D D]]
[[Category: Oikonomakos, N G]]
[[Category: Zographos, S E]]
[[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]]