2QLL

Human liver glycogen phosphorylase- GL complex

Summary for 2QLL

• Entry DOI: 10.2210/pdb2qll/pdb
• Related: 1FA9 1FC0
• Descriptor: Glycogen phosphorylase, liver form, protein targeting to glycogen - GL, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: drug discovery, glycogen metabolism, protein-protein interaction, allosteric enzyme, carbohydrate metabolism, disease mutation, glycogen storage disease, glycosyltransferase, nucleotide-binding, phosphorylation, pyridoxal phosphate, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 98102.12

Authors

Pautsch, A.,Streicher, R.,Wissdorf, O.,Stadler, N. (deposition date: 2007-07-13, release date: 2008-02-19, Last modification date: 2013-03-13)

Primary citation

Pautsch, A.,Stadler, N.,Wissdorf, O.,Langkopf, E.,Moreth, W.,Streicher, R.
Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase.
J.Biol.Chem., 283:8913-8918, 2008

PubMed Abstract: Disrupting the interaction between glycogen phosphorylase and the glycogen targeting subunit (G(L)) 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 G(L)-derived peptide. The structure reveals the C terminus of G(L) binding in a hydrophobically collapsed conformation to the allosteric regulator-binding site at the phosphorylase dimer interface. G(L) mimics interactions that are otherwise employed by the activator AMP. Functional studies show that G(L) binds tighter than AMP and confirm that the C-terminal Tyr-Tyr motif is the major determinant for G(L) binding potency. Our study validates the G(L)-phosphorylase interface as a novel target for small molecule interaction.

PubMed: 18198182
DOI: 10.1074/jbc.M706612200

Experimental method

X-RAY DIFFRACTION (2.56 Å)