Difference of Activation Processes and Structure of Activation Peptides in Human Pepsinogens A and Progastricsin

• Published in: Journal of biochemistry (Tokyo) Vol. 105; no. 1; pp. 15 - 22
• Main Authors: Kageyama, Takashi, Ichinose, Masao, Miki, Kazumasa, Athauda, Senarath B., Tanji, Masao, Takahashi, Kenji
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.1989
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid; Enzyme Activation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; Hydrolases; man; Molecular Sequence Data; Pepsin A - metabolism; Pepsinogens - metabolism; Pepstatins - metabolism; progastricsin; Protein Conformation; Human; Purification; Peptides; Gel electrophoresis; Enzyme; HPLC chromatography; Activation; Pepsinogen; PH; Models; Mechanism of action; Aminoacid sequence; Conformation
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a122610

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-Val45 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.