Enzymatic inactivation of human alpha 1-antichymotrypsin by metalloproteinases in snake venoms of the family Elapidae.
Incubation of dialyzed Elapid venoms with the human plasma proteinase inhibitor, alpha 1-antichymotrypsin, resulted in enzymatic inactivation of the inhibitor by metalloproteinases in the crude venoms. Dendroaspis angusticeps venom exhibited the highest activity on alpha 1-antichymotrypsin. However, venoms from seven genera inactivated the inhibitor, indicating that the metalloproteinases responsible for the inactivation are widespread among snakes of the family Elapidae. Electrophoretic analysis revealed that intact alpha 1-antichymotrypsin (64,000 daltons) was converted to a 60,000 dalton inactive inhibitor. No stable complexes between alpha 1-antichymotrypsin and venom proteinases were observed, and no random proteolysis of the inhibitor occurred. The Elapid venoms showed little or no proteolytic activity on casein or hide powder azure, confirming observations from other laboratories. However, all venoms tested completely inactivated native alpha 1-antichymotrypsin by limited proteolysis.
D000818:Animals; D002364:Caseins / Q000378:metabolism; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008666:Metalloendopeptidases; D013997:Time Factors; D000514:alpha 1-Antichymotrypsin
D002364:Caseins; D004546:Elapid Venoms; D000514:alpha 1-Antichymotrypsin; D004492:Edetic Acid; D010450:Endopeptidases; D002918:Chymotrypsin; D008666:Metalloendopeptidases