Disease relevance of fructose-1,6-bisphosphate

• BACKGROUND: Glycerol kinase (GK) from Escherichia coli is a velocity-modulated (V system) enzyme that has three allosteric effectors with independent mechanisms: fructose-1,6-bisphosphate (FBP); the phosphocarrier protein IIAGlc; and adenosine nucleotides [1].

High impact information on fructose-1,6-bisphosphate

• The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate (FBP) has been determined to a resolution of 2.82 A [2].
• The simultaneous binding of Mg(2+), PEP, and FBP to YPK is favored by 3.21 kcal/mol compared to independent binding [3].
• In the yPK-Tl-Mn-FBP complex, a Tl+-Mn2+ distance of 6.0 +/- 0.1 A is observed, indicating that FBP causes a conformational change at the active site in the absence of PEP [4].
• On the other hand, in the presence of 5 mM glucose, the level of FBP in spermatids increased markedly, while that of ATP declined rapidly [5].
• FBP (0.35 microM) was required for 50% activation of PK, when the PK activity was measured at 25 microM PEP and 0.2 mM ADP [5].

Biological context of fructose-1,6-bisphosphate

• Three novel compounds were identified that effect the allosteric regulation of YPK by FBP and/or act as novel allosteric activators of the enzyme [6].
• We have analyzed the structural determinants of the allosteric activation of yeast pyruvate kinase (YPK) by mutational and kinetic analysis and initiated a structure-based design project to identify novel effectors that modulate its allosteric response by binding to the allosteric site for fructose-1,6-bisphosphate (FBP) [6].

Anatomical context of fructose-1,6-bisphosphate

• The activator effect of fructose 1,6-bisphosphate (FBP) was found only in erythrocytes [7].

Associations of fructose-1,6-bisphosphate with other chemical compounds

• The binding interactions of PEP, Mg(2+), and FBP were monitored by fluorescence spectroscopy [3].
• Yeast pyruvate kinase (YPK) is regulated by intermediates of the glycolytic pathway [e.g., phosphoenolpyruvate (PEP), fructose 1,6-bisphosphate (FBP), and citrate] and by the ATP charge of the cell [3].

Gene context of fructose-1,6-bisphosphate

• The active site of hPKM2 is in a partially closed conformation most likely resulting from a ligand-induced domain closure promoted by the binding of FBP [2].

References