Fructose bisphosphatase ( EC 22.214.171.124) is an enzyme that converts fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis and the Calvin cycle which are both anabolic pathways. Fructose bisphosphatase catalyses the reverse of the reaction which is catalysed by phosphofructokinase in glycolysis. [1 ] These enzymes only catalyse the reaction in one direction each, and are regulated by metabolites such as [2 ] fructose 2,6-bisphosphate so that high activity of one of the two enzymes is accompanied by low activity of the other. More specifically, fructose 2,6-bisphosphate allosterically inhibits fructose 1,6-bisphosphatase, but activates phosphofructokinase-I. Fructose 1,6-bisphosphatase is involved in many different metabolic pathways and found in most organisms. FBPase requires metal ions for catalysis ( Mg 2+ and Mn 2+ being preferred) and the enzyme is potently inhibited by Li +.
fold of fructose-1,6-bisphosphatase from pig 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 ]
Three different groups of FBPases have been identified in
eukaryotes and bacteria (FBPase I-III). None of these groups have been found in [5 ] archaea so far, though a new group of FBPases (FBPase IV) which also show inositol monophosphatase activity has recently been identified in archaea. [6 ]
A new group of FBPases (FBPase V) is found in
thermophilic archaea and the hyperthermophilic bacterium . Aquifex aeolicus The characterised members of this group show strict [7 ] substrate specificity for FBP and are suggested to be the true FBPase in these organisms. [7 ] A [8 ] structural study suggests that FBPase V has a novel fold for a sugar phosphatase, forming a four-layer alpha-beta-beta-alpha sandwich, unlike the more usual five-layered alpha-beta-alpha-beta-alpha arrangement. The arrangement of the [8 ] catalytic side chains and metal ligands was found to be consistent with the three-metal ion assisted catalysis mechanism proposed for other FBPases.
The fructose 1,6-bisphosphatases found within the
Firmicutes (low GC Gram-positive bacteria) do not show any significant sequence similarity to the enzymes from other organisms. The enzyme is inhibited by Bacillus subtilis AMP, though this can be overcome by phosphoenolpyruvate, and is dependent on Mn(2+). [9 ] [10 ] Mutants lacking this enzyme are apparently still able to grow on gluconeogenic growth substrates such as malate and glycerol.
Interactive pathway map [ edit ]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1 ]
Glycolysis and Gluconeogenesis
See also [ edit ]
References [ edit ]
^ Marcus F, Harrsch PB (May 1990). "Amino acid sequence of spinach chloroplast fructose-1,6-bisphosphatase". Arch. Biochem. Biophys. 279 (1): 151–7. doi: 10.1016/0003-9861(90)90475-E. PMID 2159755.
^ Marcus F, Gontero B, Harrsch PB, Rittenhouse J (March 1986). "Amino acid sequence homology among fructose-1,6-bisphosphatases". Biochem. Biophys. Res. Commun. 135 (2): 374–81. doi: 10.1016/0006-291X(86)90005-7. PMID 3008716.
^ Zhang Y, Liang JY, Lipscomb WN (February 1993). "Structural similarities between fructose-1,6-bisphosphatase and inositol monophosphatase". Biochem. Biophys. Res. Commun. 190 (3): 1080–3. doi: 10.1006/bbrc.1993.1159. PMID 8382485.
^ York JD, Ponder JW, Majerus PW (May 1995). "Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure". Proc. Natl. Acad. Sci. U.S.A. 92 (11): 5149–53. doi: 10.1073/pnas.92.11.5149. PMC 41866. PMID 7761465.
^ Donahue JL, Bownas JL, Niehaus WG, Larson TJ (October 2000). "Purification and characterization of glpX-encoded fructose 1, 6-bisphosphatase, a new enzyme of the glycerol 3-phosphate regulon of Escherichia coli". J. Bacteriol. 182 (19): 5624–7. doi: 10.1128/jb.182.19.5624-5627.2000. PMC 111013. PMID 10986273.
^ Stec B, Yang H, Johnson KA, Chen L, Roberts MF (November 2000). "MJ0109 is an enzyme that is both an inositol monophosphatase and the 'missing' archaeal fructose-1,6-bisphosphatase". Nat. Struct. Biol. 7 (11): 1046–50. doi: 10.1038/80968. PMID 11062561.
^ a b Rashid N, Imanaka H, Kanai T, Fukui T, Atomi H, Imanaka T (August 2002). "A novel candidate for the true fructose-1,6-bisphosphatase in archaea". J. Biol. Chem. 277 (34): 30649–55. doi: 10.1074/jbc.M202868200. PMID 12065581.
^ a b Nishimasu H, Fushinobu S, Shoun H, Wakagi T (June 2004). "The first crystal structure of the novel class of fructose-1,6-bisphosphatase present in thermophilic archaea". Structure 12 (6): 949–59. doi: 10.1016/j.str.2004.03.026. PMID 15274916.
^ Fujita Y, Freese E (June 1979). "Purification and properties of fructose-1,6-bisphosphatase of Bacillus subtilis". J. Biol. Chem. 254 (12): 5340–9. PMID 221467.
^ Fujita Y, Yoshida K, Miwa Y, Yanai N, Nagakawa E, Kasahara Y (August 1998). "Identification and expression of the Bacillus subtilis fructose-1, 6-bisphosphatase gene (fbp)". J. Bacteriol. 180 (16): 4309–13. PMC 107433. PMID 9696785.
Further reading [ edit ]
External links [ edit ]
This article incorporates text from the public domain Pfam and InterPro IPR000146
This article incorporates text from the public domain Pfam and InterPro IPR009164
This article incorporates text from the public domain Pfam and InterPro IPR002803