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

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+)...

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Main Authors: Dariusz Rakus, Agnieszka Gizak, Andrzej A Kasprzak, Marek Zarzycki, Ewa Maciaszczyk-Dziubinska, Andrzej Dzugaj
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3795747?pdf=render
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author Dariusz Rakus
Agnieszka Gizak
Andrzej A Kasprzak
Marek Zarzycki
Ewa Maciaszczyk-Dziubinska
Andrzej Dzugaj
author_facet Dariusz Rakus
Agnieszka Gizak
Andrzej A Kasprzak
Marek Zarzycki
Ewa Maciaszczyk-Dziubinska
Andrzej Dzugaj
author_sort Dariusz Rakus
collection DOAJ
description 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.
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spelling doaj.art-5761eb16d9744d608d8296b7a3ab48fa2022-12-22T03:01:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7666910.1371/journal.pone.0076669The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.Dariusz RakusAgnieszka GizakAndrzej A KasprzakMarek ZarzyckiEwa Maciaszczyk-DziubinskaAndrzej DzugajThe 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.http://europepmc.org/articles/PMC3795747?pdf=render
spellingShingle Dariusz Rakus
Agnieszka Gizak
Andrzej A Kasprzak
Marek Zarzycki
Ewa Maciaszczyk-Dziubinska
Andrzej Dzugaj
The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
PLoS ONE
title The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
title_full The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
title_fullStr The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
title_full_unstemmed The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
title_short The mechanism of calcium-induced inhibition of muscle fructose 1,6-bisphosphatase and destabilization of glyconeogenic complex.
title_sort mechanism of calcium induced inhibition of muscle fructose 1 6 bisphosphatase and destabilization of glyconeogenic complex
url http://europepmc.org/articles/PMC3795747?pdf=render
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