1l7x
From Proteopedia
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|PDB= 1l7x |SIZE=350|CAPTION= <scene name='initialview01'>1l7x</scene>, resolution 2.30Å | |PDB= 1l7x |SIZE=350|CAPTION= <scene name='initialview01'>1l7x</scene>, resolution 2.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=CFF:CAFFEINE'>CFF</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1l5q|1L5Q]], [[1l5r|1L5R]], [[1l5s|1L5S]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7x OCA], [http://www.ebi.ac.uk/pdbsum/1l7x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l7x RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=232700 232700]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Soeller, W C.]] | [[Category: Soeller, W C.]] | ||
[[Category: Treadway, J L.]] | [[Category: Treadway, J L.]] | ||
| - | [[Category: 700]] | ||
| - | [[Category: CFF]] | ||
| - | [[Category: MRD]] | ||
| - | [[Category: NBG]] | ||
| - | [[Category: PLP]] | ||
[[Category: phosphorylase]] | [[Category: phosphorylase]] | ||
[[Category: purine site]] | [[Category: purine site]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:59:18 2008'' |
Revision as of 18:59, 30 March 2008
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Related: | 1L5Q, 1L5R, 1L5S
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700
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.
About this Structure
1L7X is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 21:59:18 2008
