2f3u: Difference between revisions

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-[[Image:2f3u.gif|left|200px]]<br /><applet load="2f3u" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2f3u, resolution 1.93&Aring;" />
-'''Crystal Structure of the glycogen phosphorylase B / N-(beta-D-glucopyranosyl)-N'-cyclopropyl oxalamide complex'''<br />
-==Overview==
+==Crystal Structure of the glycogen phosphorylase B / N-(beta-D-glucopyranosyl)-N'-cyclopropyl oxalamide complex==
-Five oxalyl derivatives of beta-d-glucopyranosylamine were synthesized as, potential inhibitors of glycogen phosphorylase (GP). The compounds 1-4, were competitive inhibitors of rabbit muscle GPb (with respect to, alpha-d-glucose-1-phosphate) with K(i) values of 0.2-1.4 mM, while, compound 5 was not effective up to a concentration of 10 mM. In order to, elucidate the structural basis of their inhibition, we analysed the, structures of compounds 1-4 in complex with GPb at 1.93-1.96 Angstrom, resolution. The complex structures reveal that the inhibitors can be, accommodated at the catalytic site at approximately the same position as, alpha-d-glucose and stabilize the T-state conformation of the 280 s loop, by making several favourable contacts to Asp283 and Asn284 of this loop., Comparison with the lead compound N-acetyl-beta-d-glucopyranosylamine (6), shows that the hydrogen bonding interaction of the amide nitrogen with the, main-chain carbonyl oxygen of His377 is not present in these complexes., The differences observed in the K(i) values of the four analogues can be, interpreted in terms of subtle conformational changes of protein residues, and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interactions, conformational entropy and, desolvation effects.
+<StructureSection load='2f3u' size='340' side='right'caption='[[2f3u]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2f3u]] 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=2F3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F3U FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8GP:N-(BETA-D-GLUCOPYRANOSYL)-N-CYCLOPROPYL+OXALAMIDE'>8GP</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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=2f3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3u OCA], [https://pdbe.org/2f3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f3u RCSB], [https://www.ebi.ac.uk/pdbsum/2f3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3u ProSAT]</span></td></tr>
+</table>
+== 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.
+== 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/f3/2f3u_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/main_output.php?pdb_ID=2f3u ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Five oxalyl derivatives of beta-d-glucopyranosylamine were synthesized as potential inhibitors of glycogen phosphorylase (GP). The compounds 1-4 were competitive inhibitors of rabbit muscle GPb (with respect to alpha-d-glucose-1-phosphate) with K(i) values of 0.2-1.4 mM, while compound 5 was not effective up to a concentration of 10 mM. In order to elucidate the structural basis of their inhibition, we analysed the structures of compounds 1-4 in complex with GPb at 1.93-1.96 Angstrom resolution. The complex structures reveal that the inhibitors can be accommodated at the catalytic site at approximately the same position as alpha-d-glucose and stabilize the T-state conformation of the 280 s loop by making several favourable contacts to Asp283 and Asn284 of this loop. Comparison with the lead compound N-acetyl-beta-d-glucopyranosylamine (6) shows that the hydrogen bonding interaction of the amide nitrogen with the main-chain carbonyl oxygen of His377 is not present in these complexes. The differences observed in the K(i) values of the four analogues can be interpreted in terms of subtle conformational changes of protein residues and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interactions, conformational entropy and desolvation effects.
-==About this Structure==
+Binding of oxalyl derivatives of beta-d-glucopyranosylamine to muscle glycogen phosphorylase b.,Hadjiloi T, Tiraidis C, Chrysina ED, Leonidas DD, Oikonomakos NG, Tsipos P, Gimisis T Bioorg Med Chem. 2006 Jun 1;14(11):3872-82. Epub 2006 Feb 7. PMID:16464598<ref>PMID:16464598</ref>
-F3U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with PLP and 8GP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F3U OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Binding of oxalyl derivatives of beta-d-glucopyranosylamine to muscle glycogen phosphorylase b., Hadjiloi T, Tiraidis C, Chrysina ED, Leonidas DD, Oikonomakos NG, Tsipos P, Gimisis T, Bioorg Med Chem. 2006 Jun 1;14(11):3872-82. Epub 2006 Feb 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16464598 16464598]
+</div>
+<div class="pdbe-citations 2f3u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Oryctolagus cuniculus]]
-[[Category: Phosphorylase]]
+[[Category: Leonidas DD]]
-[[Category: Single protein]]
+[[Category: Oikonomakos NG]]
-[[Category: Leonidas, D.D.]]
-[[Category: Oikonomakos, N.G.]]
-[[Category: 8GP]]
-[[Category: PLP]]
-[[Category: glycogenolysis]]
-[[Category: type 2 diabetes]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:20:54 2007''