InterPro: IPR020548 Fructose-1,6-bisphosphatase, active site

This entry represents fructose-1,6-bisphosphatase (FBPase), a critical regulatory enzyme in gluconeogenesis that catalyses the removal of 1-phosphate from fructose 1,6-bis-phosphate to form fructose 6-phosphate [1, 2]. It is involved in many different metabolic pathways and found in most organisms. FBPase requires metal ions for catalysis (Mg²⁺ and Mn²⁺ being preferred) and the enzyme is potently inhibited by Li⁺. The fold of fructose-1,6-bisphosphatase was noted to be identical to that of inositol-1-phosphatase (IMPase) [3]. Inositol polyphosphate 1-phosphatase (IPPase), IMPase and FBPase share a sequence motif (Asp-Pro-Ile/Leu-Asp-Gly/Ser-Thr/Ser) which has been shown to bind metal ions and participate in catalysis. This motif is also found in the distantly-related fungal, bacterial and yeast IMPase homologues. It has been suggested that these proteins define an ancient structurally conserved family involved in diverse metabolic pathways, including inositol signalling, gluconeogenesis, sulphate assimilation and possibly quinone metabolism [4].

In mammalian FBPase, a lysine residue has been shown to be involved in the catalytic mechanism [5]. The region around this residue is highly conserved and can be used as a signature pattern for FBPase and sedoheptulose-1,7-bisphosphatase (SBPase) an enzyme found plant chloroplasts and in photosynthetic bacteria that is functionally and structurally related to FBPase [6]. SBPase catalyses the hydrolysis of sedoheptulose 1,7-bisphosphate to sedoheptulose 7-phosphate, a step in the Calvin's reductive pentose phosphate cycle. This signature contains the active site lysine, however, it must be noted that, in some bacterial FBPase sequences, the active site lysine is replaced by an arginine.