The structural basis for neutrophil inactivation of C1̅ inhibitor

Abstract
Limited proteolysis of C.ovrhdot.1 inhibitor (C.ovrhdot.1-INH) by neutrophil elastase, Pseudomonas elastase and snake venoms resulted in initial cleavage wihin the molecule''s N-terminus followed by further cleavage within the molecule''s C-terminally placed reactive centre. N-Terminal proteolysis occurred at peptide bonds 14-15 36-37 and 40-41. This had no effect on either the inhibitory activity or the heat-stability of C.ovrhdot.1-INH. Proteolysis within the reactive centre occurred at peptide bonds 439-440, 440-441, 441-442 and 442-443. Cleavage at anyone of these sites inactivated C.ovrhdot.1-INH and conferred enhanced heat-stability upon a previously heat-labile molecule. Released neutrophil proteinases also cleaved and inactivated C.ovrhdot.1-INH, suggesting that they may physiologically regulate C.ovrhdot.1-INH during inflammatory episodes.