1h5u
From Proteopedia
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| - | [[Image:1h5u.gif|left|200px]]<br /><applet load="1h5u" size=" | + | [[Image:1h5u.gif|left|200px]]<br /><applet load="1h5u" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1h5u, resolution 1.76Å" /> | caption="1h5u, resolution 1.76Å" /> | ||
'''THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG'''<br /> | '''THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1H5U 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 GLC, CHI and PLP 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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http:// | + | 1H5U 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 <scene name='pdbligand=GLC:'>GLC</scene>, <scene name='pdbligand=CHI:'>CHI</scene> and <scene name='pdbligand=PLP:'>PLP</scene> 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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H5U OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:46:49 2008'' |
Revision as of 07:46, 3 February 2008
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THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG
Overview
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 Structure
1H5U is a Single protein structure of sequence from Oryctolagus cuniculus with , and as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
Reference
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
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