FIGURE 1

Catalytic site and allosteric site inhibition of caspases. (a) The viral inhibitors, CrmA and p35, as well as synthetic peptidic inhibitors for example, z-VAD-fmk, bind as pseudosubstrates to the active catalytic sites (solid circles) of target caspases thereby inhibiting their catalytic activity. (b) Following zymogen activation caspases are in equilibrium between active (allosteric site closed) and 'zymogen-like' inactive (allosteric site open) conformations. Compound 34 (triangle) binds to the open allosteric site in the dimeric interface thereby trapping the enzyme in an inactive state. Inactive catalytic sites are represented with open circles. For simplicity only caspase monomers are shown. See text for details