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

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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.