Interaction of calmodulin with muscle phosphofructokinase. Changes of the aggregation state, conformation and catalytic activity of the enzyme.
Phosphofructokinase from muscle has been shown to be a calmodulin-binding protein [Mayr, G.W. and Heilmeyer, L.M.G., Jr (1983) FEBS Lett. 159, 51-57]. Details of the influence of calmodulin on the aggregation state, the conformation and the catalytic properties of phosphofructokinase have been studied by enzymatic and light-scattering analyses. Calmodulin acts as a Ca2+-dependent hysteretic inhibitor of the highly active enzyme. At least one mole of calmodulin binds to each protomer of the enzyme, induces a shift from the highly active tetrameric towards an inactive dimeric state and slowly changes the conformation of the dimers. Dissociation of calmodulin from conformationally changed dimers by removal of Ca2+ stops the inactivation. Without a significant regain of catalytic activity large polymers are rapidly formed. For a reactivation of the inactivated enzyme, calmodulin has to remain associated and the incubation conditions must be changed in a way to allow for a back isomerization and reassociation of dimers. The isomerization reaction is promoted by Mg . ATP, the reassociation reaction most effectively by fructose bisphosphate. A model for the calmodulin-phosphofructokinase interaction is proposed.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology; D002384:Catalysis; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004793:Enzyme Reactivators; D004800:Enzymes, Immobilized; D005635:Fructosediphosphates / Q000494:pharmacology; D008956:Models, Chemical; D009132:Muscles / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits
D002147:Calmodulin; D004793:Enzyme Reactivators; D004800:Enzymes, Immobilized; D005635:Fructosediphosphates; C027652:fructose 2,6-diphosphate; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1