1uzu
GLYCOGEN PHOSPHORYLASE B IN COMPLEX WITH INDIRUBIN-5'-SULPHONATE
|
OverviewOverview
The binding of indirubin-5-sulphonate (E226), a potential anti-tumour, agent and a potent inhibitor (IC(50) = 35 nm) of cyclin-dependent kinase 2, (CDK2) and glycogen phosphorylase (GP) has been studied by kinetic and, crystallographic methods. Kinetic analysis revealed that E226 is a, moderate inhibitor of GPb (K(i) = 13.8 +/- 0.2 micro m) and GPa (K(i) =, 57.8 +/- 7.1 micro m) and acts synergistically with glucose. To explore, the molecular basis of E226 binding we have determined the crystal, structure of the GPb/E226 complex at 2.3 A resolution. Structure analysis, shows clearly that E226 binds at the purine inhibitor site, where caffeine, and flavopiridol also bind [Oikonomakos, N.G., Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E. & Johnson, L.N. (2000) J. Biol., ... [(full description)]
About this StructureAbout this Structure
1UZU is a [Single protein] structure of sequence from [Oryctolagus cuniculus] with PLP and INR as [ligands]. Active as [Phosphorylase], with EC number [2.4.1.1]. Structure known Active Site: PLP. Full crystallographic information is available from [OCA].
ReferenceReference
Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex., Kosmopoulou MN, Leonidas DD, Chrysina ED, Bischler N, Eisenbrand G, Sakarellos CE, Pauptit R, Oikonomakos NG, Eur J Biochem. 2004 Jun;271(11):2280-90. PMID:15153119
Page seeded by OCA on Tue Oct 30 11:21:36 2007