1l5r: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1l5r |SIZE=350|CAPTION= <scene name='initialview01'>1l5r</scene>, resolution 2.10Å | |PDB= 1l5r |SIZE=350|CAPTION= <scene name='initialview01'>1l5r</scene>, resolution 2.10Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</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>, <scene name='pdbligand=RBF:RIBOFLAVINE'>RBF</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.4.1 2.4.4.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.4.1 2.4.4.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1l5q|1L5Q]], [[1l5s|1L5S]], [[1l7x|1L7X]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l5r OCA], [http://www.ebi.ac.uk/pdbsum/1l5r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l5r RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==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. | ||
==About this Structure== | ==About this Structure== | ||
| Line 39: | Line 39: | ||
[[Category: Soeller, W C.]] | [[Category: Soeller, W C.]] | ||
[[Category: Treadway, J L.]] | [[Category: Treadway, J L.]] | ||
[[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 21:58:26 2008'' | ||
Revision as of 21:58, 30 March 2008
| |||||||
| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Activity: | Transferase, with EC number 2.4.4.1 | ||||||
| Related: | 1L5Q, 1L5S, 1L7X
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human liver glycogen phosphorylase a complexed with riboflavin, N-Acetyl-beta-D-Glucopyranosylamine and CP-403,700
OverviewOverview
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 StructureAbout this Structure
1L5R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 21:58:26 2008