1l7x
From Proteopedia
(New page: 200px<br /> <applet load="1l7x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l7x, resolution 2.30Å" /> '''Human liver glycoge...) |
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| - | [[Image:1l7x.gif|left|200px]]<br /> | + | [[Image:1l7x.gif|left|200px]]<br /><applet load="1l7x" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1l7x" size=" | + | |
caption="1l7x, resolution 2.30Å" /> | caption="1l7x, resolution 2.30Å" /> | ||
'''Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700'''<br /> | '''Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of | + | Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of glycogen to maintain serum glucose levels and is a therapeutic target for diabetes. HLGP is regulated by multiple interacting allosteric sites, each of which is a potential drug binding site. We used surface plasmon resonance (SPR) to screen for compounds that bind to the purine allosteric inhibitor site. We determined the affinities of a series of compounds and solved the crystal structures of three representative ligands with K(D) values from 17-550 microM. The crystal structures reveal that the affinities are partly determined by ligand-specific water-mediated hydrogen bonds and side chain movements. These effects could not be predicted; both crystallographic and SPR studies were required to understand the important features of binding and together provide a basis for the design of new allosteric inhibitors targeting this site. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1L7X 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 NBG, PLP, 700, CFF and MRD 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:// | + | 1L7X 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=NBG:'>NBG</scene>, <scene name='pdbligand=PLP:'>PLP</scene>, <scene name='pdbligand=700:'>700</scene>, <scene name='pdbligand=CFF:'>CFF</scene> and <scene name='pdbligand=MRD:'>MRD</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=1L7X OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carty, M | + | [[Category: Carty, M D.]] |
[[Category: Culp, J.]] | [[Category: Culp, J.]] | ||
| - | [[Category: Danley, D | + | [[Category: Danley, D E.]] |
| - | [[Category: Day, Y | + | [[Category: Day, Y S.N.]] |
| - | [[Category: Ekstrom, J | + | [[Category: Ekstrom, J L.]] |
| - | [[Category: Fletterick, R | + | [[Category: Fletterick, R J.]] |
| - | [[Category: Gibbs, E | + | [[Category: Gibbs, E M.]] |
| - | [[Category: Hoover, D | + | [[Category: Hoover, D J.]] |
| - | [[Category: Myszka, D | + | [[Category: Myszka, D G.]] |
| - | [[Category: Pauly, T | + | [[Category: Pauly, T A.]] |
| - | [[Category: Rath, V | + | [[Category: Rath, V L.]] |
| - | [[Category: Soeller, W | + | [[Category: Soeller, W C.]] |
| - | [[Category: Treadway, J | + | [[Category: Treadway, J L.]] |
[[Category: 700]] | [[Category: 700]] | ||
[[Category: CFF]] | [[Category: CFF]] | ||
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[[Category: purine site]] | [[Category: purine site]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:42:17 2008'' |
Revision as of 11:42, 21 February 2008
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Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700
Contents |
Overview
Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of glycogen to maintain serum glucose levels and is a therapeutic target for diabetes. HLGP is regulated by multiple interacting allosteric sites, each of which is a potential drug binding site. We used surface plasmon resonance (SPR) to screen for compounds that bind to the purine allosteric inhibitor site. We determined the affinities of a series of compounds and solved the crystal structures of three representative ligands with K(D) values from 17-550 microM. The crystal structures reveal that the affinities are partly determined by ligand-specific water-mediated hydrogen bonds and side chain movements. These effects could not be predicted; both crystallographic and SPR studies were required to understand the important features of binding and together provide a basis for the design of new allosteric inhibitors targeting this site.
Disease
Known disease associated with this structure: Glycogen storage disease VI OMIM:[232700]
About this Structure
1L7X 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.
Reference
Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase., Ekstrom JL, Pauly TA, Carty MD, Soeller WC, Culp J, Danley DE, Hoover DJ, Treadway JL, Gibbs EM, Fletterick RJ, Day YS, Myszka DG, Rath VL, Chem Biol. 2002 Aug;9(8):915-24. PMID:12204691
Page seeded by OCA on Thu Feb 21 13:42:17 2008
Categories: Homo sapiens | Phosphorylase | Single protein | Carty, M D. | Culp, J. | Danley, D E. | Day, Y S.N. | Ekstrom, J L. | Fletterick, R J. | Gibbs, E M. | Hoover, D J. | Myszka, D G. | Pauly, T A. | Rath, V L. | Soeller, W C. | Treadway, J L. | 700 | CFF | MRD | NBG | PLP | Purine site
