title: The origin of the high sensitivity of muscle fructose 1,6-bisphosphatase towards AMP.
abstract: Adenosine 5'-monophosphate (AMP) inhibits muscle fructose 1,6-bisphosphatase (FBPase) about 44 times stronger than the liver isozyme. The key role in strong AMP binding to muscle isozyme play K20, T177 and Q179. Muscle FBPase which has been mutated towards the liver enzyme (K20E/T177M/Q179C) is inhibited by AMP about 26 times weaker than the wild-type muscle enzyme, but it binds the fluorescent AMP analogue, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP), similarly to the wild-type liver enzyme. The reverse mutation of liver FBPase towards the muscle isozyme significantly increases the affinity of the mutant to TNP-AMP. High affinity to the inhibitor but low sensitivity to AMP of the liver triple mutant suggest differences between the isozymes in the mechanism of allosteric signal transmission.
authors.affiliation: Department of Animal Physiology, Institute of Zoology, Wroclaw University, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Rakus
authors.forename: E
authors.initials: E
authors.lastname: Maciaszczyk
authors.forename: D
authors.initials: D
authors.lastname: Wawrzycka
authors.forename: S
authors.initials: S
authors.lastname: Ułaszewski
authors.forename: K
authors.initials: K
authors.lastname: Eschrich
authors.forename: A
authors.initials: A
authors.lastname: Dzugaj
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000494:Allosteric Regulation / Q000235:genetics; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology*; D009154:Mutation
chemical_list: D000596:Amino Acids; D007527:Isoenzymes; D000249:Adenosine Monophosphate; C036744:2',3'-O (2,4,6-trinitrocyclohexadienylidine)adenosine 5'-monophosphate; D006597:Fructose-Bisphosphatase