Rakus D, Maciaszczyk E, Wawrzycka D, Ułaszewski S, Eschrich K, Dzugaj A
Department of Animal Physiology, Institute of Zoology, Wroclaw University, Poland.
FEBS Lett. 2005 Oct 24;579(25):5577-81. doi: 10.1016/j.febslet.2005.09.021. Epub 2005 Sep 28.
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.
5'-单磷酸腺苷（AMP）对肌肉果糖1,6-二磷酸酶（FBPase）的抑制作用比对肝脏同工酶的抑制作用强约44倍。K20、T177和Q179在AMP与肌肉同工酶的紧密结合中起关键作用。已向肝脏酶发生突变的肌肉FBPase（K20E/T177M/Q179C）受AMP抑制的程度比野生型肌肉酶弱约26倍，但它与荧光AMP类似物2',3'-O-（2,4,6-三硝基苯基）腺苷5'-单磷酸（TNP-AMP）的结合情况与野生型肝脏酶相似。肝脏FBPase向肌肉同工酶的反向突变显著增加了突变体对TNP-AMP的亲和力。肝脏三重突变体对抑制剂的高亲和力但对AMP的低敏感性表明同工酶在变构信号传递机制上存在差异。
