Kerfelec B, Cambillau C, Puigserver A, Chapus C
Eur J Biochem. 1986 Jun 16;157(3):531-8. doi: 10.1111/j.1432-1033.1986.tb09699.x.
Subunit III has so far been found only in the pancreas of ruminants in a non-covalent association (procarboxypeptidase A-S6) with two different proteins: the procarboxypeptidase A itself (subunit I) and a C-type chymotrypsinogen (subunit II). In contrast with these latter two proteins, which are zymogens of pancreatic proteases, subunit III seems to be devoid of any activity towards specific substrates of pancreatic proteases. However, it possesses a weakly functional active site which allows it to hydrolyze a non-specific ester, p-nitrophenyl acetate, and to react with several active-site titrants. The binding of proflavin to subunit III shows that this protein owns a non-polar binding site with a very high Kd compared to that of chymotrypsin. The comparison of the amino acid sequences of subunit III and some serine proteases showed that subunit III is closely related to an elastase. Models of the tertiary structure of subunit III suggest a conformational modification that affects the substrate binding and could explain the lack of specific enzymatic activity. The presence of subunit III in the ternary complex is not related to an enzymatic function. This protein does not participate in the activation process of subunit I but prevents the denaturation of this subunit at low pH. This may represent its biological role in the acidic environment of the duodenum in ruminants.
迄今为止，亚基III仅在反刍动物的胰腺中被发现，它与两种不同的蛋白质以非共价结合的形式存在（羧肽酶原A-S6）：羧肽酶原A本身（亚基I）和一种C型胰凝乳蛋白酶原（亚基II）。与后两种作为胰腺蛋白酶原的蛋白质不同，亚基III似乎对胰腺蛋白酶的特定底物没有任何活性。然而，它具有一个功能较弱的活性位点，能够水解一种非特异性酯——对硝基苯乙酸，并能与几种活性位点滴定剂发生反应。原黄素与亚基III的结合表明，与胰凝乳蛋白酶相比，该蛋白质拥有一个解离常数（Kd）非常高的非极性结合位点。亚基III与一些丝氨酸蛋白酶的氨基酸序列比较表明，亚基III与弹性蛋白酶密切相关。亚基III的三级结构模型表明存在一种构象修饰，这种修饰影响底物结合，并且可以解释其缺乏特异性酶活性的原因。亚基III在三元复合物中的存在与酶功能无关。该蛋白质不参与亚基I的激活过程，但能防止该亚基在低pH值下变性。这可能代表了它在反刍动物十二指肠酸性环境中的生物学作用。
