Regulation of glycogen phosphorylase. Role of the peptide region surrounding the phosphoserine residue in determining enzyme properties.
A phosphopeptide which contains 14 residues including phosphoserine and which is derived from the NH2-terminal region of skeletal muscle glycogen phosphorylase (Nolan, C., Novoa, W. B., Krebs, E. G., and Fischer, E. H. (1964) Biochemistry 3, 542-551) has been shown to induce the enzymic properties of phosphorylase a in phosphorylase b and b'. When phosphorylase b is incubated with the phosphorylated tetradecapeptide, the following changes occur: (1) the enzyme becomes partially catalytically active in the absence of AMP; (2) the allosteric interactions of the enzyme are altered, as evidenced by the fact that phosphorylase b does not bind AMP cooperatively, and is no longer inhibited by glucose-6-P; and (3) the enzyme, normally present as a dimer, associates to a tetramer. Phosphorylase b' is a modified form of phosphorylase in which the phosphorylation site has been removed by limited tryptic attack. In the presence of phosphopeptide, 86% of the total enzyme activity can be induced in the absence of AMP. The properties of phosphorylases b and b' with phosphopeptide, cited above, are all characteristics of the phosphonenzyme, phosphorylase a. In addition, evidence is presented that these effects are specific. They are not the result of the polycationic nature of the peptide since they cannot be duplicated by spermine, and the phosphate group must also be present for the peptide to effect changes on the enzyme.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000494:Allosteric Regulation; D000818:Animals; D005958:Glucosephosphates / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D009943:Organophosphorus Compounds; D010455:Peptides / Q000494:pharmacology; D010748:Phosphopeptides / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D006005:Phosphorylases / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits; D012694:Serine / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology; D014461:Ultracentrifugation
D005958:Glucosephosphates; D009943:Organophosphorus Compounds; D010455:Peptides; D010748:Phosphopeptides; D010761:Phosphorus Radioisotopes; D013096:Spermine; D000249:Adenosine Monophosphate; D012694:Serine; D006005:Phosphorylases