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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 Ca(2+) affects conformation of the catalytic loop 52-72 of muscle FBPase and inhibits its activity by competing with activatory divalent cations, e.g. Mg(2+) and Zn(2+). We also propose the molecular mechanism of Ca(2+)-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 Ca(2+) stabilizes the disengaged-like form of the loop.

SUBMITTER: Rakus D 

PROVIDER: S-EPMC3795747 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.

Rakus Dariusz D   Rakus Dariusz D   Gizak Agnieszka A   Kasprzak Andrzej A AA   Zarzycki Marek M   Maciaszczyk-Dziubinska Ewa E   Dzugaj Andrzej A  

PloS one 20131011 10


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 Ca(2+) affects conformation of the catalytic loop 52-72 of muscle FBPase and inhibits its activity by competing with activatory divalent cations, e.g. Mg(2+) and Zn(2+). We also propose the molecular mechani  ...[more]

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