[HTML][HTML] Identification of fructose 6-phosphate-and fructose 1-phosphate-binding residues in the regulatory protein of glucokinase
M Veiga-da-Cunha, E Van Schaftingen - Journal of Biological Chemistry, 2002 - ASBMB
Glucokinase is inhibited in the liver by a regulatory protein (GKRP) whose effects are
increased by Fru-6-P and suppressed by Fru-1-P. To identify the binding site of these
phosphate esters, we took advantage of the homology of GKRP to the isomerase domain of
GlmS (glucosamine-6-phosphatesynthase) and created 12 different mutants of rat GKRP.
Mutations of three residues predicted to bind to Fru-6-P resulted in proteins that were∼ 5-
fold (S110A) and 50-fold (S179A and K514A) less potent as inhibitors of glucokinase and …
increased by Fru-6-P and suppressed by Fru-1-P. To identify the binding site of these
phosphate esters, we took advantage of the homology of GKRP to the isomerase domain of
GlmS (glucosamine-6-phosphatesynthase) and created 12 different mutants of rat GKRP.
Mutations of three residues predicted to bind to Fru-6-P resulted in proteins that were∼ 5-
fold (S110A) and 50-fold (S179A and K514A) less potent as inhibitors of glucokinase and …