2qll | pdb_00002qll
Human liver glycogen phosphorylase- GL complex
Structural highlights
DiseasePYGL_HUMAN Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.[1] FunctionPYGL_HUMAN Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDisrupting 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. Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase.,Pautsch A, Stadler N, Wissdorf O, Langkopf E, Moreth W, Streicher R J Biol Chem. 2008 Apr 4;283(14):8913-8. Epub 2008 Jan 15. PMID:18198182[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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