The structure of the Mg 2+ -dependent enzyme human phosphoserine phosphatase (HPSP) was exploited to examine the structural and functional role of the divalent cation in the active site of phosphatases. Most interesting is the biochemical observation that a Ca 2+ ion inhibits the activity of HPSP, even in the presence of added Mg 2+ .The sixfold coordinated Mg 2+ ion present in the active site of HPSP under normal physiological conditions, was replaced by a Ca 2+ ion by using a crystallization conditionwith high concentration of CaCl2(). .