1l5r: Difference between revisions
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|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> | |||
}} | }} | ||
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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. | ||
==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: phosphorylase]] | [[Category: phosphorylase]] | ||
[[Category: purine site]] | [[Category: purine site]] | ||
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