The origin of the high sensitivity of muscle fructose 1,6-bisphosphatase towards AMP

• Published in: FEBS letters 2005-10, Vol.579 (25), p.5577-5581
• Main Authors: Rakus, D., Maciaszczyk, E., Wawrzycka, D., Ułaszewski, S., Eschrich, K., Dzugaj, A.
• Format: Article
• Language: English
• Subjects: 2′,3′-O-(2,4,6-trinitrophenyl)adenosine 5′-monophosphate; Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - pharmacology; Allosteric inhibition; Allosteric Regulation - genetics; Amino Acid Sequence; Amino Acids - genetics; AMP binding; F1,6-P2; F2,6-P2; FBPase; fructose 1,6-bisphosphatase; fructose 1,6-bisphosphate; fructose 2,6-bisphosphate; Fructose-Bisphosphatase - antagonists & inhibitors; Fructose-Bisphosphatase - genetics; Glyconeogenesis; Humans; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Liver - enzymology; Molecular Sequence Data; Muscle FBPase; Muscles - enzymology; Mutation; PFK; phosphofructokinase; TNP-AMP
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.09.021

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.