1fa9: Difference between revisions
New page: left|200px<br /> <applet load="1fa9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fa9, resolution 2.4Å" /> '''HUMAN LIVER GLYCOGEN... |
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'''HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH AMP'''<br /> | '''HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH AMP'''<br /> | ||
==Overview== | ==Overview== | ||
Glycogen phosphorylases catalyze the breakdown of glycogen to | Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate, which enters glycolysis to fulfill the energetic requirements of the organism. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target. To support inhibitor design, we determined the crystal structures of the active and inactive forms of human liver glycogen phosphorylase a. During activation, forty residues of the catalytic site undergo order/disorder transitions, changes in secondary structure, or packing to reorganize the catalytic site for substrate binding and catalysis. Knowing the inactive and active conformations of the liver enzyme and how each differs from its counterpart in muscle phosphorylase provides the basis for designing inhibitors that bind preferentially to the inactive conformation of the liver isozyme. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1FA9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLC, AMP 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] Full crystallographic information is available from [http:// | 1FA9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GLC:'>GLC</scene>, <scene name='pdbligand=AMP:'>AMP</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FA9 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ammirati, M.]] | [[Category: Ammirati, M.]] | ||
[[Category: Danley, D | [[Category: Danley, D E.]] | ||
[[Category: Fennell, K | [[Category: Fennell, K F.]] | ||
[[Category: Hynes, T | [[Category: Hynes, T R.]] | ||
[[Category: LeMotte, P | [[Category: LeMotte, P K.]] | ||
[[Category: Mansour, M | [[Category: Mansour, M N.]] | ||
[[Category: Pandit, J.]] | [[Category: Pandit, J.]] | ||
[[Category: Rath, V | [[Category: Rath, V L.]] | ||
[[Category: Schulte, G | [[Category: Schulte, G K.]] | ||
[[Category: Wasilko, D | [[Category: Wasilko, D J.]] | ||
[[Category: AMP]] | [[Category: AMP]] | ||
[[Category: GLC]] | [[Category: GLC]] | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:35 2008'' | ||
Revision as of 13:36, 21 February 2008
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HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH AMP
OverviewOverview
Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate, which enters glycolysis to fulfill the energetic requirements of the organism. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target. To support inhibitor design, we determined the crystal structures of the active and inactive forms of human liver glycogen phosphorylase a. During activation, forty residues of the catalytic site undergo order/disorder transitions, changes in secondary structure, or packing to reorganize the catalytic site for substrate binding and catalysis. Knowing the inactive and active conformations of the liver enzyme and how each differs from its counterpart in muscle phosphorylase provides the basis for designing inhibitors that bind preferentially to the inactive conformation of the liver isozyme.
DiseaseDisease
Known disease associated with this structure: Glycogen storage disease VI OMIM:[232700]
About this StructureAbout this Structure
1FA9 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core., Rath VL, Ammirati M, LeMotte PK, Fennell KF, Mansour MN, Danley DE, Hynes TR, Schulte GK, Wasilko DJ, Pandit J, Mol Cell. 2000 Jul;6(1):139-48. PMID:10949035
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