a-d-Glucose activates glucokinase (EC ) on its binding to the active site by inducing a global hysteretic conformational change. Using intrinsic tryptophan fluorescence as a probe on the a-d-glucose induced conforma-tional changes in the pancreatic isoform 1 of human glucokinase, key resi-dues involved in the process were identified by site-directed mutagenesis.