α 1-Antitrypsin is the most abundant circulating protease inhibitor and the archetype of the
serine protease inhibitor or serpin superfamily. Members of this family may be inactivated by
point mutations that favor transition to a polymeric conformation. This polymeric
conformation underlies diseases as diverse as α 1-antitrypsin deficiency-related cirrhosis,
thrombosis, angio-edema, and dementia. The precise structural linkage within a polymer
has been the subject of much debate with evidence for reactive loop insertion into β-sheet A …