HUMAN PROTEINASE-INHIBITOR-9 (P19) IS A POTENT INHIBITOR OF SUBTILISIN-A

Serine proteinase inhibitors function as regulators of serine proteina se activity in a variety of physiological processes. Proteinase inhibi tor 9 (PI9) is a 42 kDa member of the ovalbumin family of serpins that is expressed in placenta, lung, and cytotoxic lymphocytes. In this st udy, wc have described the inhibitory mechanism of recombinant human P I9 towards the bacterial endoproteinase subtilisin A. PI9 inhibited th e amidolytic activity of subtilisin A via a rapid, single step mechani sm with an equilibrium inhibition constant of 3.6 pM and an overall se cond-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 regulat ed by PI9 in vivo. (C) 1997 Academic Press.