title: Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases.
abstract: 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.
mesh_terms: 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
chemical_list: 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