Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor: the possible role of enzyme-inhibitor flexibility.

A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (K(i) = 0.2 microM). Despite having a trypsin-specific arginine at the primary specificity P(1) site, it inhibits bovine chymotrypsin almost as well (K(i) = 2 microM). Furthermore, while the latter reactivity improves 10(4)-fold by the single replacement of P(1) Arg by Leu, changing P(1)' from Lys to Met only moderately improves trypsin affinity (K(i) = 30 nM). The apparent low compatibility to trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with P(1) Arg inhibit crayfish and shrimp trypsins with K(i) values in the picomolar range. This unprecedented high discrimination between orthologous enzymes is postulated to derive from flexibility differences in the protein-protein interaction. The more than four orders of magnitude phylum selectivity makes these peptides prospective candidates for agricultural use.