Analysis of the molecular mechanism of pepsinogen activation with techniques of protein chemistry

胃蛋白酶原通过释放其nh2末端44-47残基被激活为胃蛋白酶。两个高度敏感的切割位点存在于激活片段中。一个位点是激活片段和胃蛋白酶片段之间的键（P-site），另一个位点是位于激活片段中心区域的键（I-site）。当p位点首先被切割时，胃蛋白酶原直接转化为胃蛋白酶，释放完整的激活片段。另一方面，当i位点首先被切割时，产生中间形式。在这种情况下，需要进一步的裂解来完成激活，因此激活本质上是一个逐步的过程。分子内反应和分子间反应都参与了这些裂解。分子内p位点或i位点的断裂对于产生活性分子是一个重要的起始反应。然而，p位点的分子间裂解对于加速和完成活化是必不可少的。

Pepsinogen is activated to pepsin by releasing its NH2-terminal 44-47 residues. Two highly susceptible sites of cleavage are present in the activation segments. One site is the bond between the activation segment and the pepsin moiety (P-site) and the other is a bond located in the central region of the activation segment (I-site). When the P-site is cleaved first, pepsinnogen is converted to pepsin directly with the release of the intact activation segment. On the other hand, when the I-site is cleaved first, an intermediate form is generated,. In this case, further cleavages are necessary to complete the activation and therefore the activation is essentially a stepwise process. Both intramolecular and intermolecular reactions are involved in these cleavages. The intramolecular clevage of the P-site or the I-site is important as an initiating reaction to generate active molecules. However, the intermolecular cleavage of the P-site is essential to accelerate and complete the activation.