Pepsin human

The amino acid compositions vary widely and do not indicate any relationship among the enzymes. However, there is one unusual feature. In four proteins the basic amino acid content is exceptionally low. Human gastricsin and human pepsin have no lysine and contain only one histidine and three arginine residues per molecule. Porcine pepsin has one lysine, one histidine, and two arginine residues. Penicillopepsin has five lysines, three histidines, and no arginine. The significance of this unusual feature, which is not shared by other acid proteases, is not clear. 

Fig. 4. Heat inactivation of human pepsin (I) and gastricsin (II) at pH 2.0 and 3.2. The enzyme solutions were incubated for 10 minutes at the indicated temperature and the proteolytic activity measiued. The losses of activity were expressed as percent of the inactivation relative to that of the solution incubated at 45°. From Tang et al. (T6).

Fig. 24. Immunoelectrophoresis of human gastric juice. Immunoelectrophoietic patterns A, in vitro depepsinized normal gastric juice B, crystalline human pepsin C, crystalline human gastricsin D, human serum albumin E, glandular mucoprotein F, mucoproteose C, rapid vitamin Bj2 binder H, slow vitamin B 2 binder. Anti-gastric juice immune serum was used throughout. From Simons and Grasbedc (S9).

Multiple sequence alignment of BACE family members and human pepsin (Protein Data Bank entry Ipso, used as the basis of homology modeling). Identical residues are shaded gray, highly conserved residues in yellow, and active-site residues in the model in contact with the peptide substrate are indicated by an asterisk ( ). BACE residue Arg 296, which is most often serine or threonine at this position in... 

M. Fujinaga, M. M. Chernaia, N. I. Tarasova, S. C. Mosimann, M. N. G. James. Crystal structure of human pepsin and its complex with pepstatin. Prot. Science. 1995, 4, 960-972. 

Human pepsins Repetitive anion exchange chromatography Roberts and Taylor [346]... 

Fig. 4.7.4. (A) Capacity of immobilized inhibitor sorbent (e-aminocaproyl-L-Phe-D-Phe-OMe-Separon) in mg of pepsin per g of dry sorbent, and (B) portion of immobilized inhibitor molecules involved in specific complex formation (in %) with respect to immobilized inhibitor concentration (in pmol of inhibitor per g of dry sorbent). -0-, porcine pepsin chicken pepsin, and human pepsin.

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

A content of carbohydrates is a theoretical possibility for heterogeneity in the gastric proteinases. Kageyama and Takahashi (37a) have shown that the carbohydrates are linked to an asparagine residue in the pepsin part of the monkey pepsinogen. At least two carbohydrate containing residues have been observed in the sequence of human pepsin (Sepulveda and Tang, personal communication). On the other hand, Stepanov (38) have reported that... 

Human pepsin C = Human gastricsin (Hum. pep. Residues 46-70 (53), residues 355-373 (54). Personal communications, P. Sepulveda and J. Found.). 

The results shown in Table I and this discussion indicate that the gastric proteases form a family of enzymes, closely related structurally. It also appears that pepsin A from different species (pig, ox and humans) are more closely related to each other than pepsin A is to other proteinases of the same species (e.g. bovine pepsin A, B, and chymosin) but with our present knowledge it is difficult to determine the interspecies relationship between bovine pepsin B and human pepsin C. 

To study its mode of inhibition, we prepared several derivatives and measured their kinetics of inhibition. Both N-acetyl-statine and N-acetyl-alanyl-statine are competitive inhibitors for pepsin with values of 1.2 X lO M and 5.65 x 10 M, respectively. The value for N-acetyl-valyl-statine is 4.8 x 10 M. These statyl derivatives, therefore, are very strong inhibitors. The value for N-acetyl-statine is 600-fold smaller than that of its structural analog N-acetyl-leucine. The derivative which contains two statyl residues in a tetrapeptide exhibits inhibitory properties which approach those of pepstatin itself. Other acid proteases, human pepsin, human gastricsin, renin, cathepsin D, the acid protease from R. chinensis and bovine chymosin, also are inhibited by pepstatin and its derivatives. We suggest that the statyl residue is responsible for the unusual inhibitory capability of pepstatin and that statine is an analog of the previously proposed transition state for catalysis by pepsin and other acid proteases. 

P. Sepulveda and J. Tang, Oklahoma Medical Research Foundation, Oklahoma City, Partial Sequences of Human Pepsin and Gastricsin . 

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