Pepsinogen amino acid sequences

Bond between leucine (Leu) at residue 44 of the sequence of the prosegment of pepsinogen and the first residue of the amino acid sequence of pepsin, isoleucine (He). 

In recent years, pepsinogens and pepsins from a number of species have been isolated and characterized. Amino acid sequencing and X-ray crystallographic studies revealed substantial homologies and similar tertiary structures of pepsinogens from different species. 

The complete amino acid sequence of porcine pepsinogen A has been determined partial structures of bovine pepsinogen A and of human pepsin are known. 

Pspsin (EC 3.4.23.1) a protease in the stomach of all vertebrates with the exception of stomachless fish (e.g. carp). Purified P. shows maximal activity at pH 1-2, but in the stomach the optimal pH is 2-4. Above pH 6, P. is inactivated by denaturation. It preferentially catalyses hydrolysis of peptide bonds between two hydrophobic amino acids (Phe-Leu, Phe-Phe, Phe-TyrT With the exception of protamines, keratin, mucin, ovomucoid and other carbohydrate-rich proteins, most proteins are attacked by P. The products of P. action are peptone, i. e. mixtures of peptides in the M range 300-3,000. P. is a highly acidic (pi 1), single chain phosphoprotein (327 amino acid residues of known primary sequence, M, 34,500), which is released from its zymogen (pepsinogen, 42,500) by autocatalysis in the presence of hydrochloric acid. 

Pepsins and Pepsinogens.—The carbohydrate compositions and some sequences of amino-acids have been determined for glycopeptides derived from pepsinogens isolated from Japanese monkeys. Glycopeptides released by successive treatments of pepsinogen I with thermolysin and aminopeptidase contained 2-amino-... 

Amino acid Protein from pepstatin + pepsinogen (molar ratio 1.4 1) Expected from sequence of residues 17-370 Protein from pepstatin + pepsinogen (molar ratio 0.9 1) Pepsin (residues 45-370)... 

Amino acid Peptide from bovine pepsinogen Expected from sequence of residues 1-17 Peptide from calf prochymosin Expected from sequence of residues 1-27 Prochymosin peptide after Bio-gel P2... 

Porcine pepsinogen apparently does not convert itself into pepsin in a one-step transformation, releasing the activation segment 1-44 intact. By difference, it would seem that the alternative, progressive activation scheme must be operative. Certainly, the amino acid composition, and the NH2- and COOH-terminal analyses on the peptide obtained from the stopped activation plus the fact that it acts like the pepsin inhibitor peptide all suggest it to have been derived from residues 1-16 in the porcine sequence. 

Figure 5. The sequence of a pepsin-inhibiting peptide formed during the activation of porcine pepsinogen. The lower sequence illustrates the proposed binding mode with Leu-12 as the residue. Below each residue is listed whether that amino acid residue has positive (+), negative (-), or neutral (n) cleavage probabilities.

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