Disease relevance of FBP

• A full-length clone of pig kidney fructose 1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) was isolated by screening a cDNA library for complementation of an Escherichia coli fbp deletion mutation [1].
• The form II fructose 1,6-bisphosphatase and phosphoribulokinase genes form part of a large operon in Rhodobacter sphaeroides: primary structure and insertional mutagenesis analysis [2].

High impact information on FBP

• Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze alpha-D-fructose 1,6-bisphosphate [3].
• Crystallographic evidence for the action of potassium, thallium, and lithium ions on fructose-1,6-bisphosphatase [3].
• Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution [4].
• The three-dimensional structure of the complex between fructose 1,6-bisphosphatase (EC 3.1.3.11) and the physiological inhibitor beta-D-fructose 2,6-bisphosphate (Fru-2,6-P2), an analogue of the substrate (fructose 1,6-bisphosphate), has been refined at 2.6-A resolution to a residual error (R) factor of 0.171 [4].
• Molecular structure of fructose-1,6-bisphosphatase at 2.8-A resolution [5].

Chemical compound and disease context of FBP

• Oxidation experiments using Escherichia coli thioredoxin, in analogy with the chloroplast FBPase system, indicate an unexpected mode of regulation for AF2372, a key phosphatase in this anaerobic sulfate reducer [6].
• As estimated from enzymatic activity and visual inspection of coomassie blue-stained SDS-PAGE gels, porcine fructose-1,6-bisphosphatase constitutes as much as 20% of the soluble protein from the over-expressing E. coli strain [7].

Biological context of FBP

• The AMP inhibition results from the relative movement between the AMP and FBP domains which distorts the active site during the transition by shifting the metal binding sites to unfavourable positions [8].
• The plasmin esterase inhibitors, epsilon-amino-n-caproic acid, tranexamic acid, and L-lysine, previously established to reverse the MMI response to MIF, FBP, and C3 activators were found to inhibit both Fc- and C3-dependent phagocytosis [9].
• Simultaneously, PCMV utilized the glycolytic intermediate [1-(13)C]fructose 1,6-bisphosphate (FBP) mainly for gluconeogenesis, producing [1-(13)C]glucose with only minor [3-(13)C]lactate production [10].
• Complete amino acid sequence of pig kidney fructose-1,6-bisphosphatase [11].
• The role of the 190's loop of fructose-1,6-bisphosphatase (Fru-1, 6-P2ase) in the allosteric regulation of Fru-1,6-P2ase has been investigated through kinetic studies on three mutant enzymes, Glu-192 --> Ala, Glu-192 --> Gln, and Asp-187 --> Ala [12].

Anatomical context of FBP

• As our recent investigation revealed, in mammalian heart muscle, fructose 1,6-bisphosphatase (FBPase)--a key enzyme of glyconeogenesis--is located around the Z-line, inside cells' nuclei and, as we demonstrate here for the first time, it associates with intercalated discs [13].
• The structures of the native fructose-1,6-bisphosphatase (Fru-1,6-Pase), from pig kidney cortex, and its fructose 2,6-bisphosphate (Fru-2,6-P2) complexes have been refined to 2.8 A resolution to R-factors of 0.194 and 0.188, respectively [14].
• In contrast to data from skeletal muscle [Gizak, A., Rakus, D. and Dzugaj, A. (2003) Histol. Histopathol. 18, 135-142], in cardiomyocytes FBPase was present not only in the cytoplasm, but surprisingly, also in the nucleus [15].
• Lack of fructose-1,6-bisphosphatase activity in LLC-PK1 cells [16].

Associations of FBP with chemical compounds

• Fructose-1,6-bisphosphatase requires a divalent metal cation for catalysis, Mg(2+) being its most studied activator [17].
• In order to provide information on the relative binding characteristics of glycolytic enzymes, the effect of fructose-1,6-bisphosphate (FBP) on the release of glycolytic enzymes from cultured pig kidney cells treated with digitonin has been studied [18].
• Alignment of the cyanogen bromide fragments was accomplished by analysis of a product of limited proteolysis by an endogenous protease and by characterization of the tryptic peptides isolated from S-[14C]carboxymethylated fructose-1,6-bisphosphatase [11].
• Identification of the highly reactive sulfhydryl group of pig kidney fructose 1,6-bisphosphatase at cysteine 128 [19].
• A comparison of the kinetic properties of native and N-ethylmaleimide-modified fructose-1,6-bisphosphatase reveals differences in some properties but none is so striking as the complete loss of fructose 2,6-bisphosphate sensitivity [20].

Regulatory relationships of FBP

• Some aspects of the proposed model may be relevant to all forms of FBPase, including the thioredoxin-regulated FBPase from the chloroplast [21].

Analytical, diagnostic and therapeutic context of FBP

• Isolation and sequence analysis of the cDNA for pig kidney fructose 1,6-bisphosphatase [1].
• Mutation of Arg-15, Glu-19, Arg-22, and Thr-27 of porcine liver fructose-1,6-bisphosphatase was carried out by site-directed mutagenesis [22].
• A mutant enzyme form of fructose-1,6-bisphosphatase, G122A, was purified and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism spectrometry (CD), and initial rate kinetics [23].
• Residues 1--10 of porcine fructose-1,6-bisphosphatase (FBPase) are poorly ordered or are in different conformations, sensitive to the state of ligation of the enzyme [21].
• Structural aspects of the allosteric inhibition of fructose-1,6-bisphosphatase by AMP: the binding of both the substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate and catalytic metal ions monitored by X-ray crystallography [24].

References