Limited proteolysis of C1-inhibitor by chymotrypsin-like proteinases.

Limited proteolysis of C1-inhibitor was observed with human skin chymase, human cathepsin G, and bovine chymotrypsin. In each case, the inhibitor was degraded to one major product migrating slightly faster than the native inhibitor in an SDS-polyacrylamide gel. The inhibitory activity of C1-inhibitor against human plasma kallikrein was not altered by the modification with chymase. Edman degradation of the proteolyzed inhibitor revealed two sequences in a 1:1 ratio: NPNATSSSQ, the N-terminus of native C1-inhibitor, and VEPILEVSSL. This second sequence showed that the Phe33-Val34 bond was hydrolyzed. Our results provide another example of the susceptibility of the N-terminal region of C1-inhibitor to proteolytic cleavage.