Mutations on the hinge region of leukocyte elastase inhibitor determine the loss of inhibitory function

Leukocyte elastase inhibitor (LEI) is a cytosolic component of lung macroph ages and blood leukocytes that inhibits neutrophil elastase. LEI is a membe r of the serpin superfamily, these proteins, mostly protease inhibitors, ar e thought to undergo a conformational change upon complex formation with pr oteinase that involves partial insertion of the hinge region of the reactiv e centre loop into a beta-sheet of the inhibitor. In this work three mutati ons were produced in the hinge region of elastase inhibitor that abolish th e inhibition activity of LEI and transform the protein in a substrate of th e elastase. This result demonstrates that the inhibitory mechanism of serpi n is common to LEI. (C) 2000 Academic Press.