Domain separation in the activation of glycogen phosphorylase a.
The crystal structure of glycogen phosphorylase a complexed with its substrates, orthophosphate and maltopentaose, has been determined and refined at a resolution of 2.8 angstroms. With oligosaccaride bound at the glycogen storage site, the phosphate ion binds at the catalytic site and causes the regulatory and catalytic domains to separate with the loss of stabilizing interactions between them. Homotropic cooperativity between the active sites of the allosteric dimer results from rearrangements in isologous contacts between symmetry-related helices in the subunit interface. The conformational changes in the core of the interface are correlated with those observed on covalent activation by phosphorylation at Ser14 (phosphorylase b----a).
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
E J
EJ
Goldsmith
S R
SR
Sprang
R
R
Hamlin
N H
NH
Xuong
R J
RJ
Fletterick
D000495:Allosteric Site; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D003461:Crystallography; D004789:Enzyme Activation; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides; D010710:Phosphates / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D005958:Glucosephosphates; D046911:Macromolecular Substances; D009844:Oligosaccharides; D010710:Phosphates; C019193:maltopentaose; D006003:Glycogen; C031590:glucose-1-phosphate; D010762:Phosphorylase a; D006005:Phosphorylases