1wv1: Difference between revisions

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-{{Seed}}
-[[Image:1wv1.png|left|200px]]
-<!--
+==Crystallographic studies on acyl ureas, a new class of inhibitors of glycogenphosphorylase. Broad specificity of the allosteric site==
-The line below this paragraph, containing "STRUCTURE_1wv1", creates the "Structure Box" on the page.
+<StructureSection load='1wv1' size='340' side='right'caption='[[1wv1]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1wv1]] 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=1WV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WV1 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BN5:5-[3-({[(2,4-DICHLOROBENZOYL)AMINO]CARBONYL}AMINO)-2-METHYLPHENOXY]PENTANOIC+ACID'>BN5</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
-{{STRUCTURE_1wv1|  PDB=1wv1  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wv1 OCA], [https://pdbe.org/1wv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wv1 RCSB], [https://www.ebi.ac.uk/pdbsum/1wv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wv1 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/wv/1wv1_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=1wv1 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Acyl ureas were discovered as a novel class of inhibitors for glycogen phosphorylase, a molecular target to control hyperglycemia in type 2 diabetics. This series is exemplified by 6-{2,6-Dichloro- 4-[3-(2-chloro-benzoyl)-ureido]-phenoxy}-hexanoic acid, which inhibits human liver glycogen phosphorylase a with an IC(50) of 2.0 microM. Here we analyze four crystal structures of acyl urea derivatives in complex with rabbit muscle glycogen phosphorylase b to elucidate the mechanism of inhibition of these inhibitors. The structures were determined and refined to 2.26 Angstroms resolution and demonstrate that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Acyl ureas induce conformational changes in the vicinity of the allosteric site. Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct inhibition of AMP binding and by indirect inhibition of substrate binding through stabilization of the T' state.
-===Crystallographic studies on acyl ureas, a new class of inhibitors of glycogenphosphorylase. Broad specificity of the allosteric site===
+Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs.,Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E Protein Sci. 2005 Jul;14(7):1760-71. PMID:15987904<ref>PMID:15987904</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1wv1" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15987904}}, adds the Publication Abstract to the page
+*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15987904 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15987904}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-WV1 is a [[Single protein]] structure of 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=1WV1 OCA].
-==Reference==
-Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs., Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E, Protein Sci. 2005 Jul;14(7):1760-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15987904 15987904]
-Acyl ureas as human liver glycogen phosphorylase inhibitors for the treatment of type 2 diabetes., Klabunde T, Wendt KU, Kadereit D, Brachvogel V, Burger HJ, Herling AW, Oikonomakos NG, Kosmopoulou MN, Schmoll D, Sarubbi E, von Roedern E, Schonafinger K, Defossa E, J Med Chem. 2005 Oct 6;48(20):6178-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16190745 16190745]
-The structure of glycogen phosphorylase b with an alkyldihydropyridine-dicarboxylic acid compound, a novel and potent inhibitor., Zographos SE, Oikonomakos NG, Tsitsanou KE, Leonidas DD, Chrysina ED, Skamnaki VT, Bischoff H, Goldmann S, Watson KA, Johnson LN, Structure. 1997 Nov 15;5(11):1413-25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9384557 9384557]
-Allosteric inhibition of glycogen phosphorylase a by the potential antidiabetic drug 3-isopropyl 4-(2-chlorophenyl)-1,4-dihydro-1-ethyl-2-methyl-pyridine-3,5,6-tricarbo xylate., Oikonomakos NG, Tsitsanou KE, Zographos SE, Skamnaki VT, Goldmann S, Bischoff H, Protein Sci. 1999 Oct;8(10):1930-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10548038 10548038]
-Identification, synthesis, and characterization of new glycogen phosphorylase inhibitors binding to the allosteric AMP site., Kristiansen M, Andersen B, Iversen LF, Westergaard N, J Med Chem. 2004 Jul 1;47(14):3537-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15214781 15214781]
 [[Category: Oryctolagus cuniculus]]
-[[Category: Phosphorylase]]
+[[Category: Chrysina ED]]
-[[Category: Single protein]]
+[[Category: Defossa E]]
-[[Category: Chrysina, E D.]]
+[[Category: Klabunde T]]
-[[Category: Defossa, E.]]
+[[Category: Kosmopoulou MN]]
-[[Category: Klabunde, T.]]
+[[Category: Leonidas DD]]
-[[Category: Kosmopoulou, M N.]]
+[[Category: Oikonomakos NG]]
-[[Category: Leonidas, D D.]]
+[[Category: Wendt KU]]
-[[Category: Oikonomakos, N G.]]
-[[Category: Wendt, K U.]]
-[[Category: Glycogenolysis]]
-[[Category: Type 2 diabetes]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 01:12:02 2008''