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1exv

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Revision as of 07:09, 20 December 2017

HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700

Structural highlights

1exv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Activity:	Phosphorylase, with EC number 2.4.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PYGL_HUMAN] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.^[1]

Function

[PYGL_HUMAN] 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

Background: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described. Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes.

Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.,Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ Chem Biol. 2000 Sep;7(9):677-82. PMID:10980448^[2]

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

References

↑ Burwinkel B, Bakker HD, Herschkovitz E, Moses SW, Shin YS, Kilimann MW. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. 1998 Apr;62(4):785-91. PMID:9529348
↑ Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ. Human liver glycogen phosphorylase inhibitors bind at a new allosteric site. Chem Biol. 2000 Sep;7(9):677-82. PMID:10980448

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700==
 <StructureSection load='1exv' size='340' side='right' caption='[[1exv]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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=1exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1exv OCA], [http://pdbe.org/1exv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1exv RCSB], [http://www.ebi.ac.uk/pdbsum/1exv 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=1exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1exv OCA], [http://pdbe.org/1exv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1exv RCSB], [http://www.ebi.ac.uk/pdbsum/1exv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1exv ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ex/1exv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ex/1exv_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 1exv" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
 == References ==
 <references/>

1exv

From Proteopedia

Revision as of 07:09, 20 December 2017

HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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