The activation of bovine pepsinogen. Sequence of the peptides released, identification of a pepsin inhibitor.

Bovine pepsinogen is converted into pepsin by removal of 45 amino acid residues from the NH, terminus of the single polypeptide chain. The complete sequence of the activation peptides has been deduced from two overlapping sets of peptides, one set obtained by autoactivation of the zymogen at pH 2 and the second set from a tryptic digest of maleylated pepsinogen. A peptide derived from the 17 residues at the NH2 terminus of bovine pepsinogen has been identified as an inhibitor of the milk-clotting action of pepsin. Extensive sequence homologies exist among the activation peptides of bovine and porcine pepsinogens and bovine prochymosin. In the peptides from the two pepsinogens, 30 of the 44 or 45 residues are identical, and most of the substitutions in the other residues are conservative. The preservation of positive charges in the NH,-terminal portion of the zymogen molecules, lost during activation, agrees with current ideas on the involvement of this segment in stabilizing the physical structure of the zymogens.