Structural studies of human muscle FBPase

Muscle fructose-1,6-bisphosphatase (FBPase), which catalyzes the hydrolysis of fructose-1,6-bisphosphate (F1,6BP) to fructose-6-phosphate (F6P) and inorganic phosphate, regulates glucose homeostasis by controlling glyconeogenic pathway. FBPase requires divalent cations, such as Mg2+, Mn2+, or Zn2+, for its catalytic activity; however, calcium ions inhibit muscle isoform interrupting movement loop. It has been shown that residue E69 in this loop plays a key role sensitivity towards ions. The study presented here is based on five crystal structures wild-type human E69Q mutant complexes with substrate product enzymatic reaction, namely F1,6BP F6P. ligands are bound active site studied proteins same manner have excellent definition electron density maps. In all crystals, homotetrameric enzyme assumes cruciform quaternary structure, κ angle, describes orientation upper dimer respect lower dimer, –85o. This unusual arrangement subunits, characteristic R-state FBPase, also observed solution small-angle X-ray scattering (SAXS).