Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases.
Human plasma serine proteinase inhibitors (serpins) gradually lost activity when incubated with catalytic amounts of snake venom or bacterial metalloproteinases. Electrophoretic analyses indicated that antithrombin III, C1-inhibitor, and alpha 2-antiplasmin had been converted by limited proteolysis into modified species which retained inhibitory activity. Further proteolytic attack resulted in the formation of inactivated inhibitors; alpha 1-proteinase inhibitor (alpha 1-antitrypsin) and alpha 1-antichymotrypsin were also enzymatically inactivated, but active intermediates were not detected. Sequence analyses indicated that the initial, noninactivating cleavage occurred in the amino-terminal region of the inhibitors. Inactivation resulted in all cases from the limited proteolysis of a single bond near, but not at, the reactive site bond in the carboxy-terminal region of the inhibitors. The results indicate that the serpins have two regions which are susceptible to limited proteolysis--one near the amino-terminal end and another in the exposed reactive site loop of the inhibitor.
D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000378:metabolism; D001665:Binding Sites; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D003435:Crotalid Venoms / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases; D011480:Protease Inhibitors / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D003174:Complement C1 Inactivator Proteins; D003435:Crotalid Venoms; D011480:Protease Inhibitors; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D000979:alpha-2-Antiplasmin; D000990:Antithrombin III; D010450:Endopeptidases; D008666:Metalloendopeptidases