Inhibitory serinových proteáz serpinového TYPU inhibující cysteinové proteázy: příklad „cross-class“ inhibice

Proteolytic enzymes are classified into four mechanistic classes: serine, cysteine, aspartic proteases, and metalloproteinases, respectively. Active proteases of each class may be inhibited by a class-specific group of proteinaceous inhibitors. The most common serine-type proteinase inhibitors are called sepins. Leukocyte elastase, the blood clottingand blood clot dissolving enzymes, to name some, belong to the target serine proteases. During evolution, some serpine-like molecules lost their enzyme inhibitory action, others changed their properties, and a specific group of serpins gained an abberant inhibitory against cysteine proteinases. The first of such „cross-class“ serpine inhibitors identified was crmA (cytokine response modifier), inhibiting interleukin-1 beta converting enzyme (ICE), a cysteine protease implicated in the promotion of inflammatory reaction and apoptosis upon a cow-pox virus infection. A dozen other cross-class inhibitory serpins has been identified so far, and found to be involved in the process of apoptosis, protein processing, embryonic development, cancerogenesis and inflammation. The molecular basis of the cysteine protease inhibition by serpins appars to be analogous with serine protease inhibition by serpins, namely a stable enzyme-serpin complex formation.