title: The glucoamylase inhibitor acarbose is a direct activator of phosphorylase kinase.
abstract: Phosphorylase kinase (PhK), an (alphabetagammadelta)(4) complex, stimulates energy production from glycogen in the cascade activation of glycogenolysis. Its large homologous alpha and beta subunits regulate the activity of the catalytic gamma subunit and account for 81% of PhK's mass. Both subunits are thought to be multidomain structures, and recent predictions based on their sequences suggest the presence of potentially functional glucoamylase (GH15)-like domains near their amino termini. We present the first experimental evidence of such a domain in PhK by demonstrating that the glucoamylase inhibitor acarbose binds PhK, perturbs its structure, and stimulates its kinase activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Owen W
authors.initials: OW
authors.lastname: Nadeau
authors.forename: Weiya
authors.initials: W
authors.lastname: Liu
authors.forename: Igor G
authors.initials: IG
authors.lastname: Boulatnikov
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Sage
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Peters
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Carlson
mesh_terms: D020909:Acarbose / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors*; D006801:Humans; D007004:Hypoglycemic Agents; D010764:Phosphorylase Kinase / Q000737:chemistry* / Q000187:drug effects; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D010764:Phosphorylase Kinase; D005087:Glucan 1,4-alpha-Glucosidase; D020909:Acarbose