Apoptosis or programmed cell death (PCD), a cellular process that functions to remove mutated or damaged cells from an organism, has been extensively studied in eukaryotes. This research has indicated that caspase proteins have a prominent role in the initiation of PCD. Unlike metazoan organisms or vertebrates, caspase genes are not found in plants, fungi, and protozoa. These organisms contain metacaspases which are homologous to caspases in structure, sequence and function. Initial research has suggested that metacaspases share a similar role to caspases where their proteolytic activity aids in the initiation PCD. However, unlike caspases, metacaspases are unique in that they can only be activated by the presence of calcium ions. The focus of this research is to determine an accurate molecular model for calcium-dependent activation of Type I metacaspases from the fungus Schizophyllum commune. Kinetic activity assays were employed to determine metacaspase activity in response to exposure to various divalent metallic cations, while differential scanning fluorimetry was used to characterize the binding of these cations to the Type I metacaspases. These experimental techniques were used to obtain information regarding the ligand binding and conformational shifts within the metacaspase that result in proteolytic activity. Initial results from this research have suggested that calcium significantly increases metacaspase activity, manganese moderately increases the activity, while magnesium, cobalt, and copper have no impact on metacaspase activity. Results from differential scanning fluorimetry indicated that calcium binds to the metacaspase at two different sites on the metacaspases. At one binding site, affinity for the calcium ion is significantly greater than that of the other. Furthermore, manganese has been demonstrated to bind to only one site on the metacaspase. These results, along with mutant Type I metacaspases have been employed to theorize a model for activation of the Type I metacaspase. Currently, it is predicted that during calcium activation, saturation of the high-affinity calcium-binding site occurs before the low-affinity site. However, once the low-affinity site is saturated, an active site loop undergoes a conformational shift which promotes proteolytic activity.