Lazure C, Leduc R, Seidah N G, Thibault G, Genest J, Chrétien M
Nature. 1984;307(5951):555-8. doi: 10.1038/307555a0.
Tonin, an esteroprotease isolated from rat submaxillary 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 enzyme. 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 beta-lipotropin (beta-LPH), adrenocorticotropin (ACTH), pro-opiomelanocortin (POMC) and substance P. 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, gamma-subunit of nerve growth factor (NGF) and the recently described gamma-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.
托宁是从大鼠颌下腺分离出的一种酯蛋白酶，是一种具有胰蛋白酶和胰凝乳蛋白酶样活性的丝氨酸蛋白酶。托宁的底物特异性表明它不同于激肽释放酶，肯定不是肾素样酶或血管紧张素转换酶。托宁可通过切割苯丙氨酸 - 组氨酸键，直接从血管紧张素I、血管紧张素原和肾素的合成十四肽底物产生血管活性肽血管紧张素II。还发现它能切割各种底物中的一些苯丙氨酸和精氨酸键，如β-促脂素（β-LPH）、促肾上腺皮质激素（ACTH）、阿片促黑激素皮质素原（POMC）和P物质。在此，我们描述大鼠颌下腺托宁的完整氨基酸序列。将219个氨基酸的序列与其他丝氨酸蛋白酶，特别是激肽释放酶、神经生长因子（NGF）的γ亚基和最近描述的γ-肾素进行比较，发现有广泛的相似性。更有趣的是，它还揭示了丝氨酸蛋白酶活性位点三联体（天冬氨酸、组氨酸、丝氨酸）中通常存在的一个天冬氨酸残基被一个亮氨酸残基取代。这种不寻常的取代似乎并不影响该酶的蛋白水解活性。
