Inactivation and reactivation of phosphoprotein phosphatase of rabbit skeletal muscle.  Role of ATP and divalent metal ions.
The regulatory mechanism of a phosphoprotein phosphatase (EC 3.1.3.16), which is considered to catalyze the dephosphorylation reaction of several phosphoproteins (glycogen synthetase-D (EC 2.4.1.11), phospho-form of phosphorylase b kinase (EC 2.7.1.38), phosphohistone and phosphorylase a (EC 2.4.1.1)), was studied with partially purified preparations from rabbit skeletal muscle.  Time- and temperature-dependent inactivation and reactivation of phosphohistone phosphatase, as well as phosphorylase phosphatase (EC 3.1.3.17), were observed on pre0incubation of the enzyme(s) with ATP, and subsequent incubation with divalent metal ions (Mg2+, Mn2+, or Co2+) without any change of molecular size.  Manganese, however, instantly restored the activity of the ATP-inactivated enzyme, and increased the maximal velocity of the enzyme while decreasing its affinity to phosphorylase a.  However, the metal ion inhibited the reactivated enzyme competively with respect to phosphorylase a.  It is suggested that phosphoprotein phosphatase(s) is a metalloenzyme, and that ATP results in a conformational change of the enzyme protein in such a way that a metal ion can be easily released due to the chelating effect of ATP, or incorporated (in the presence of excess metal ions) into the enzyme protein.
D000255:Adenosine Triphosphate; D000818:Animals; D002413:Cations, Divalent; D055598:Chemical Phenomena; D002621:Chemistry; D003035:Cobalt; D004492:Edetic Acid; D004789:Enzyme Activation; D006006:Glycogen Synthase / Q000378:metabolism; D006657:Histones; D008274:Magnesium; D008345:Manganese; D008670:Metals; D009132:Muscles / Q000201:enzymology*; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010764:Phosphorylase Kinase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D011817:Rabbits; D013696:Temperature; D013997:Time Factors
D002413:Cations, Divalent; D006657:Histones; D008670:Metals; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D003035:Cobalt; D008345:Manganese; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D006005:Phosphorylases; D006006:Glycogen Synthase; D010764:Phosphorylase Kinase; D010744:Phosphoric Monoester Hydrolases; D008274:Magnesium