title: 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.
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rakus
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gizak
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Kasprzak
authors.forename: Marek
authors.initials: M
authors.lastname: Zarzycki
authors.forename: Ewa
authors.initials: E
authors.lastname: Maciaszczyk-Dziubinska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dzugaj
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005260:Female; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors*; D005943:Gluconeogenesis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D050505:Mutant Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000187:drug effects / Q000201:enzymology; D013050:Spectrometry, Fluorescence; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
chemical_list: D050505:Mutant Proteins; D006597:Fructose-Bisphosphatase; D002118:Calcium