Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases

Abstract

Tonin¹, an ester protease isolated from rat sub maxillary gland, is a serine protease with trypsin-and chymotrypsin-like activity. The substrate specificity of tonin shows that it differs from kallikreins and is definitely not a renin-like enzyme or an angiotensin-converting enzyme². Tonin can produce directly the vasoactive peptide angiotensin II, from angiotensin I, angiotensinogen and the synthetic tetradecapeptide substrate of renin by cleavage of a Phe-His bond. It has also been found to cleave some Phe and Arg bonds in various substrates such as β-lipotropin (β-LPH), adrenocorticotropin (ACTH), proopiomelanocortin (POMC)³ and substance P⁴. Here we describe the complete amino acid sequence of rat submaxillary gland, tonin. Comparison of the sequence of 219 amino acids with other serine proteases, particularly kallikreins, γ-subunit of nerve growth factor (NGF) and the recently described γ-renin, reveals extensive similarities. More interestingly, it also reveals the substitution of an Asp residue always found in the serine protease active site triad (Asp, His, Ser) by a Leu residue. This unusual substitution does not seem to affect the proteolytic activity of the enzyme.