THE PRIMARY ELASTASE INHIBITOR (ELASTASIN) AND TRYPSIN-INHIBITOR (CONTRAPSIN) IN THE GOAT ARE SERPINS RELATED TO HUMAN ALPHA(1)-ANTI-CHYMOTRYPSIN

Two primary serine proteinase inhibitors in goat plasma have been isol ated and characterized. The N-terminal sequence analysis of the purifi ed proteins revealed that they are closely related to each other and a re highly homologous to human alpha(1)-anti-chymotrypsin rather than a lpha(1)-proteinase inhibitor. However, despite structural similarities the inhibitory specificity of the goat inhibitors differed from each other and from that of anti-chymotrypsin. In contrast with human anti- chymotrypsin, one of the goat inhibitors was shown to be a strong and specific inhibitor of trypsin (k(ass.) = 1.9 x 10(6) M(-1).s(-1)), whe reas the other was an efficient inhibitor of neutrophil elastase (k(as s.) = 1.5 x 10(6) M(-1).s(-1)). Differences in the inhibitory specific ity of each protein could readily be attributed to the amino acid sequ ence within the reactive site region. The trypsin inhibitor with an as sumed arginine residue at the P-1 position of the reactive-site peptid e bond is referred to as 'contrapsin', and indicates that the occurren ce of contrapsins is not restricted to rodents. In contrast, the inhib itory specificity, resistance to oxidative and proteolytic inactivatio n and the presence of a P-1 leucine residue in the elastase inhibitor is unique among inhibitory serpins that have been characterized to dat e. Because this serpin is apparently the major elastase inhibitor in g oat plasma, it is likely to be involved in the control of goat neutrop hil elastase. Therefore, we suggest the name 'elastasin', and extend i t to any other anti-chymotrypsin related serpins possessing neutrophil -elastase-inhibitory activity.