1l5s: Difference between revisions

[[Image:1l5s.gif|left|200px]]<br /><applet load="1l5s" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1L5S 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=URC:'>URC</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=1L5S OCA].  

[[Category: Carty, M D.]]

[[Category: Danley, D E.]]

[[Category: Day, Y S.N.]]

[[Category: Ekstrom, J L.]]

[[Category: Fletterick, R J.]]

[[Category: Gibbs, E M.]]

[[Category: Hoover, D J.]]

[[Category: Myszka, D G.]]

[[Category: Pauly, T A.]]

[[Category: Rath, V L.]]

[[Category: Soeller, W C.]]

[[Category: Treadway, J L.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:37 2008''