SERPIN-LIKE PROPERTIES OF ALPHA-1-ANTITRYPSIN PORTLAND TOWARDS FURIN CONVERTASE

Recent studies hale demonstrated that a serpin variant, alpha(1)-antit rypsin Portland (AT-PDX), can inhibit the mammalian convertase furin, Here, we examine the mechanism by which this inhibition takes place. W e find that furin, which does not belong to the trypsin-like serine pr otease family, the usual targets of serpins, forms an SDS-heat denatur ation-resistant complex with AT-PDX both in vitro and in vivo. AT-PDX inhibited furin with an association rate constant (k(ass)) of 1.5 x 10 (6) M-1 s(-1) which is similar to K-ass values reported for serpins wi th trypsin-like enzymes. These results illustrate that AT can be modif ied to act essentially as a suicide inhibitor of furin, an enzyme of t he subtilase superfamily of serine proteases, (C) 1998 Federation of E uropean Biochemical Societies.