Human proteinase inhibitor 9 (P19) is a potent inhibitor of subtilisin A

Serine proteinase inhibitors function as regulators of serine proteinase activity in a variety of physiological processes. Proteinase inhibitor 9 (PI9) is a 42 kDa member of the ovalbumin family of serpins that is expressed in placenta, lung, and cytotoxic lymphocytes. In this study, wc have described the inhibitory mechanism of recombinant human PI9 towards the bacterial endoproteinase subtilisin A. PI9 inhibited the amidolytic activity of subtilisin A via a rapid, single step mechanism with an equilibrium inhibition constant of 3.6 pM and an overall second-order association rate constant of 2.4 x 10(6) M(-1)s(-1), which is the strongest inhibitory mechanism of PI9 that has been described. The inhibitory action of PI9 towards subtilisin as a model proteinase may yield some indication of potential proteinases that may be regulated by PI9 in vivo. (C) 1997 Academic Press.