The Mechanism of Calcium-Induced Inhibition of Muscle Fructose 1,6-bisphosphatase and Destabilization of Glyconeogenic Complex

Abstract

The mechanism by which calcium inhibits the activity of muscle fructose 1,6-bisphosphatase (FBPase) and destabilizes its interaction with aldolase, regulating glycogen synthesis from non-carbohydrates in skeletal muscle is poorly understood. In the current paper, we demonstrate evidence that Ca2+ affects conformation of the catalytic loop 52-72 of muscle FBPase and inhibits its activity by competing with activatory divalent cations, e.g. Mg2+ and Zn2+. We also propose the molecular mechanism of Ca2+-induced destabilization of the aldolase-FBPase interaction, showing that aldolase associates with FBPase in its active form, i.e. with loop 52-72 in the engaged conformation, while Ca2+ stabilizes the disengaged-like form of the loop. © 2013 Rakus et al.