1h5u: Difference between revisions

Revision as of 18:28, 2 May 2008

THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG

OverviewOverview

CP320626, a potential antidiabetic drug, inhibits glycogen phosphorylase in synergism with glucose. To elucidate the structural basis of synergistic inhibition, we determined the structure of muscle glycogen phosphorylase b (MGPb) complexed with both glucose and CP320626 at 1.76 A resolution, and refined to a crystallographic R value of 0.211 (R(free)=0.235). CP320626 binds at a novel allosteric site, which is some 33 A from the catalytic site, where glucose binds. The high resolution structure allows unambiguous definition of the conformation of the 1-acetyl-4-hydroxy-piperidine ring supported by theoretical energy calculations. Both CP320626 and glucose promote the less active T-state, thereby explaining their synergistic inhibition. Structural comparison of MGPb--glucose--CP320626 complex with liver glycogen phosphorylase a (LGPa) complexed with a related compound (CP403700) show that the ligand binding site is conserved in LGPa.

About this StructureAbout this Structure

1H5U is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.

ReferenceReference

The 1.76 A resolution crystal structure of glycogen phosphorylase B complexed with glucose, and CP320626, a potential antidiabetic drug., Oikonomakos NG, Zographos SE, Skamnaki VT, Archontis G, Bioorg Med Chem. 2002 May;10(5):1313-9. PMID:11886794 Page seeded by OCA on Fri May 2 18:28:18 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1h5u.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1h5u |SIZE=350|CAPTION= <scene name='initialview01'>1h5u</scene>, resolution 1.76&Aring;
+The line below this paragraph, containing "STRUCTURE_1h5u", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=CHI:Chi/Cp320626+Binding+Site'>CHI</scene>, <scene name='pdbsite=GLC:Glc+Binding+Site+For+Chain+A'>GLC</scene> and <scene name='pdbsite=PLP:Plp+Binding+Site+For+Chain+A'>PLP</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CHI:5-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID+[1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE'>CHI</scene>, <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5&#39;-PHOSPHATE'>PLP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1h5u|  PDB=1h5u  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h5u OCA], [http://www.ebi.ac.uk/pdbsum/1h5u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h5u RCSB]</span>
-}}
 '''THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG'''
@@ Line 30: / Line 27: @@
 [[Category: Skamnaki, V T.]]
 [[Category: Zographos, S E.]]
-[[Category: central cavity]]
+[[Category: Central cavity]]
-[[Category: drug binding site]]
+[[Category: Drug binding site]]
-[[Category: glycogen metabolism]]
+[[Category: Glycogen metabolism]]
-[[Category: glycogen phosphorylase b]]
+[[Category: Glycogen phosphorylase b]]
-[[Category: inhibition]]
+[[Category: Inhibition]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:28:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:58:21 2008''