Serine Protease Inhibitors - Cross-class Inhibitors

Cross-class Inhibitors

Most inhibitory serpins target chymotrypsin-like serine proteases (see Table 1 and Figure 2). These enzymes are defined by the presence of a nucleophilic serine residue in their catalytic site. Examples include thrombin, trypsin, and human neutrophil elastase.

Some serpins inhibit other classes of protease and are termed "cross-class inhibitors". A number of such serpins have been shown to target cysteine proteases. These enzymes differ from serine proteases in that they are defined by the presence of a nucleophilic cysteine residue, rather than a serine residue, in their catalytic site. Nonetheless, the enzymatic chemistry is similar, and serpins most likely inhibit both classes of enzyme in a similar fashion.

Examples of cross-class inhibitory serpins include squamous cell carcinoma antigen 1 (SCCA-1) and the avian serpin myeloid and erythroid nuclear termination stage-specific protein (MENT) both inhibit papain-like cysteine proteases

The viral serpin crmA is a suppressor of the inflammatory response through inhibition of IL-1 and IL-18 processing by the cysteine protease caspase-1. In eukaryotes, a plant serpin has been shown to inhibit metacaspases and a papain-like cysteine protease. It is presently unclear whether any mammalian serpins function to inhibit caspases in vivo.