Primary structure and functional properties of cobra (Naja naja naja) venom Kunitz‐type trypsin inhibitor

A trypsin inhibitor from the venom of the cobra Naja naja naja has been isolated by a single step of reverse‐phase high‐performance liquid chromatography. The protein strongly inhibits trypsin (Ki= 3.5 pM). The primary structure was determined by peptide analysis of the [14C]carboxymethylated inhibitor. The 57‐residue polypeptide chain belongs to the family of Kunitz‐type inhibitors, and exhibits 42% residue identity with bovine pancreatic trypsin inhibitor. The structure shows only 70% identity with the corresponding peptide from the Capa cobra (Naja nevia), establishing that the inhibitor molecule exhibits extensive variations. Functionally, a basic residue at position P3′ correlates with strong inhibition.