title: Three-dimensional structure of phosphorylase kinase at 22 A resolution and its complex with glycogen phosphorylase b.
abstract: Phosphorylase kinase (PhK) integrates hormonal and neuronal signals and is a key enzyme in the control of glycogen metabolism. PhK is one of the largest of the protein kinases and is composed of four types of subunit, with stoichiometry (alphabetagammadelta)(4) and a total MW of 1.3 x 10(6). PhK catalyzes the phosphorylation of inactive glycogen phosphorylase b (GPb), resulting in the formation of active glycogen phosphorylase a (GPa) and the stimulation of glycogenolysis. We have determined the three-dimensional structure of PhK at 22 A resolution by electron microscopy with the random conical tilt method. We have also determined the structure of PhK decorated with GPb at 28 A resolution. GPb is bound toward the ends of each of the lobes with an apparent stoichiometry of four GPb dimers per (alphabetagammadelta)(4) PhK. The PhK/GPb model provides an explanation for the formation of hybrid GPab intermediates in the PhK-catalyzed phosphorylation of GPb.
authors.affiliation: Laboratory of Molecular Biophysics, Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. venien@biop.ox.ac.uk
authors.forename: Catherine
authors.initials: C
authors.lastname: Vénien-Bryan
authors.forename: Edward M
authors.initials: EM
authors.lastname: Lowe
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boisset
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Traxler
authors.forename: Louise N
authors.initials: LN
authors.lastname: Johnson
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Carlson
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D024982:Glycogen Phosphorylase, Muscle Form / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron / Q000379:methods; D008954:Models, Biological; D010764:Phosphorylase Kinase / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology
chemical_list: D024982:Glycogen Phosphorylase, Muscle Form; D010764:Phosphorylase Kinase