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1wv0

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Revision as of 16:12, 11 April 2018

Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site

Structural highlights

1wv0 is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3amv, 1wut, 1wvy, 1wv1
Activity:	Phosphorylase, with EC number 2.4.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E. Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs. Protein Sci. 2005 Jul;14(7):1760-71. PMID:15987904 doi:14/7/1760

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wv0"

@@ Line 1: / Line 1: @@
 ==Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site==
 <StructureSection load='1wv0' size='340' side='right' caption='[[1wv0]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3amv|3amv]], [[1wut|1wut]], [[1wvy|1wvy]], [[1wv1|1wv1]]</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=1wv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wv0 OCA], [http://pdbe.org/1wv0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wv0 RCSB], [http://www.ebi.ac.uk/pdbsum/1wv0 PDBsum]</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=1wv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wv0 OCA], [http://pdbe.org/1wv0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wv0 RCSB], [http://www.ebi.ac.uk/pdbsum/1wv0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wv0 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/1wv0_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/1wv0_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1wv0

From Proteopedia

Revision as of 16:12, 11 April 2018

Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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