title: Difference of activation processes and structure of activation peptides in human pepsinogens A and progastricsin.
abstract: The activation processes of two human pepsinogens A (pepsinogens 3 and 5) and progastricsin were compared with special attention to pepsinogens 3 and 5. Each zymogen was converted to pepsin in a stepwise manner through intermediate forms. In pepsinogens A, the major cleavage site was the Leu23-Lys24 bond and this cleavage was suggested to occur intramolecularly. When each of the pepsins A was added to the corresponding pepsinogen A exogenously, the latter was rapidly converted to pepsin, releasing the 47-residue intact activation segment. In this case, the Leu47-Val48 bond connecting the activation segment with the pepsin moiety was cleaved by an intermolecular reaction. On the other hand, when the pepsinogen A-pepstatin complex was attacked by each corresponding pepsin A added exogenously, significant cleavage by an intermolecular reaction occurred at the Asp25-Phe26 bond, generating the Phe26-intermediate form. These shifts of the cleavage sites in pepsinogens A depending on the activation conditions are likely to correlate with the conformation of the activation segment. These results can be explained consistently in terms of a proposed molecular model of activation.
authors.affiliation: Department of Biochemistry, Primate Research Institute, Kyoto University, Aichi.
authors.forename: T
authors.initials: T
authors.lastname: Kageyama
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: K
authors.initials: K
authors.lastname: Miki
authors.forename: S B
authors.initials: SB
authors.lastname: Athauda
authors.forename: M
authors.initials: M
authors.lastname: Tanji
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000378:metabolism; D010435:Pepsinogens / Q000378:metabolism*; D010436:Pepstatins / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D010435:Pepsinogens; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D010434:Pepsin A; C031375:pepstatin