Molecular Recognition of the Protein Phosphatase 1 Glycogen Targeting Subunit by Glycogen Phosphorylase

@article{citeulike:3214181, abstract = {Disrupting the interaction between glycogen phosphorylase and the glycogen targeting subunit (GL) of protein phosphatase 1 is emerging as a novel target for the treatment of type 2 diabetes. To elucidate the molecular basis of binding, we have determined the crystal structure of liver phosphorylase bound to a GL-derived peptide. The structure reveals the C terminus of GL binding in a hydrophobically collapsed conformation to the allosteric regulator-binding site at the phosphorylase dimer interface. GL mimics interactions that are otherwise employed by the activator AMP. Functional studies show that GL binds tighter than AMP and confirm that the C-terminal Tyr-Tyr motif is the major determinant for GL binding potency. Our study validates the GL-phosphorylase interface as a novel target for small molecule interaction. 10.1074/jbc.M706612200}, author = {Pautsch, Alexander and Stadler, Nadja and Wissdorf, Oliver and Langkopf, Elke and Moreth, Werner and Streicher, Rudiger}, citeulike-article-id = {3214181}, doi = {10.1074/jbc.M706612200}, journal = {J. Biol. Chem.}, keywords = {crystallography, new, phosphatase-1}, month = {April}, number = {14}, pages = {8913--8918}, posted-at = {2008-09-10 23:20:34}, priority = {5}, title = {Molecular Recognition of the Protein Phosphatase 1 Glycogen Targeting Subunit by Glycogen Phosphorylase}, url = {http://dx.doi.org/10.1074/jbc.M706612200}, volume = {283}, year = {2008} }

TY - JOUR ID - citeulike:3214181 L3 - citeulike-article-id:3214181 N2 - Disrupting the interaction between glycogen phosphorylase and the glycogen targeting subunit (GL) of protein phosphatase 1 is emerging as a novel target for the treatment of type 2 diabetes. To elucidate the molecular basis of binding, we have determined the crystal structure of liver phosphorylase bound to a GL-derived peptide. The structure reveals the C terminus of GL binding in a hydrophobically collapsed conformation to the allosteric regulator-binding site at the phosphorylase dimer interface. GL mimics interactions that are otherwise employed by the activator AMP. Functional studies show that GL binds tighter than AMP and confirm that the C-terminal Tyr-Tyr motif is the major determinant for GL binding potency. Our study validates the GL-phosphorylase interface as a novel target for small molecule interaction. 10.1074/jbc.M706612200 IS - 14 JF - J. Biol. Chem. EP - 8918 TI - Molecular Recognition of the Protein Phosphatase 1 Glycogen Targeting Subunit by Glycogen Phosphorylase VL - 283 SP - 8913 KW - crystallography KW - new KW - phosphatase-1 AU - Pautsch, Alexander AU - Stadler, Nadja AU - Wissdorf, Oliver AU - Langkopf, Elke AU - Moreth, Werner AU - Streicher, Rudiger PY - 2008/04/04/ UR - http://dx.doi.org/10.1074/jbc.M706612200 ER -