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  • Title: Kinetic Basis of Carbohydrate-Mediated Inhibition of Human Glucokinase by the Glucokinase Regulatory Protein.
    Author: Casey AK, Miller BG.
    Journal: Biochemistry; 2016 May 31; 55(21):2899-902. PubMed ID: 27174229.
    Abstract:
    The glucokinase regulatory protein (GKRP) is a competitive inhibitor of glucokinase (GCK), triggering its localization to the hepatocyte nucleus upon glucose deprivation. Here we establish the kinetic mechanism of GKRP action by analyzing its association with a genetically encoded, fluorescent variant of human GCK. Our results demonstrate that binding of GKRP to GCK involves two steps, formation of an initial encounter complex followed by conformational equilibration between two GKRP-GCK states. Fructose 6-phosphate, a known enhancer of GKRP action, promotes formation of the initial encounter complex via a 2.6-fold increase in kon and stabilizes the complex through a 60-fold decrease in koff.
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