INTERACTION OF HUMAN PREGNANCY-ASSOCIATED PLASMA PROTEIN-A WITH SERINE PROTEINASES

Human pregnancy-associated plasma protein A (PAPP-A) inhibited signifi cantly the proteolytic activity of bovine trypsin and human plasmin. T rypsin or plasmin treatment of PAPPA resulted in the generation of a m ajor 85 kDa component and the rapid cleavage of internal thiol esters. The results indicated that both of these serine proteinases bound in a 1:1 stoichiometry to PAPP-A. The PAPP-A-bound enzymes were found to be enzymatically active towards small synthetic substrates and inacces sible to inactivation by soybean trypsin inhibitor and alpha(1)-protei nase inhibitor. The mechanism of proteinase inhibition was likely to b e entrapment, as described for alpha(2)-macroglobulin.