Function
Fructose-1,6-bisphosphatase (FBP) is an enzyme in the glucose generating pathway which converts fructose-1,6-bisphosphate to fructose 6-phosphate (F6P)[1]. FBP activity in hibernating animals is significantly reduced[2].
- Fructose-2,6-bisphosphatase (F26BP) is the stimulator of phosphofructokinase which is a key enzyme in glycolysis[3].
- Fructose-1,6-bisphosphatase/inoitol monophosphatase (FBP/IMP) is a bifunctional enzyme[4].
Relevance
FBP inhibitors are studied as drug candidates for the treatment of diabetes type 2[5].
Disease
FBP deficiency results in hyperglycemia[6].
Structural highlights
A tricyclic potent FBP inhibitor interacts with the enzyme in a hydrophobic pocket [7] (Hydrophobic, Polar, water molecule shown as red sphere).
3D Structures of Fructose-1,6-bisphosphatase
Fructose-1,6-bisphosphatase 3D structures
- ↑ Zhang Y, Liang JY, Lipscomb WN. Structural similarities between fructose-1,6-bisphosphatase and inositol monophosphatase. Biochem Biophys Res Commun. 1993 Feb 15;190(3):1080-3. PMID:8382485
- ↑ Storey KB. Metabolic regulation in mammalian hibernation: enzyme and protein adaptations. Comp Biochem Physiol A Physiol. 1997 Dec;118(4):1115-24. PMID:9505421
- ↑ Depre C, Veitch K, Hue L. Role of fructose 2,6-bisphosphate in the control of glycolysis. Stimulation of glycogen synthesis by lactate in the isolated working rat heart. Acta Cardiol. 1993;48(1):147-64. PMID:8447185
- ↑ Johnson KA, Chen L, Yang H, Roberts MF, Stec B. Crystal structure and catalytic mechanism of the MJ0109 gene product: a bifunctional enzyme with inositol monophosphatase and fructose 1,6-bisphosphatase activities. Biochemistry. 2001 Jan 23;40(3):618-30. PMID:11170378
- ↑ van Poelje PD, Potter SC, Chandramouli VC, Landau BR, Dang Q, Erion MD. Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats. Diabetes. 2006 Jun;55(6):1747-54. PMID:16731838 doi:https://dx.doi.org/10.2337/db05-1443
- ↑ van Poelje PD, Potter SC, Erion MD. Fructose-1, 6-bisphosphatase inhibitors for reducing excessive endogenous glucose production in type 2 diabetes. Handb Exp Pharmacol. 2011;(203):279-301. doi: 10.1007/978-3-642-17214-4_12. PMID:21484576 doi:https://dx.doi.org/10.1007/978-3-642-17214-4_12
- ↑ Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T. Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638 doi:10.1016/j.bmcl.2009.12.056
