The Serpins: Evolution and Adaptation in a Family of Protease Inhibitors

The serpins are a superfamily of serine protease inhibitors that have undergone divergent evolution over a period of some 600 million years (Hunt and Dayhoff 1980; Carrell and Boswell 1986). The best-studied member of the family is the human plasma protein acantitrypsin (Carrell et al. 1982), which is now known to function primarily as an inhibitor of leucocyte lastase and for this reason is alternatively named at-proteinase inhibitor (Travis and Salvesen 1983). Here we will retain the historical name ab-breviated to antitrypsin. Antitrypsin is a characteristic member of the serpins in that it is a single-chain glycoprotein of near 400 residues that functions by forming a tight 1:1 complex with its cognate protease, neutrophil (leucocyte) elas