Interaction of human pregnancy-associated plasma protein-A with serine proteinases

Human pregnancy-associated plasma protein A (PAPP-A) inhibited significantly the proteolytic activity of bovine trypsin and human plasmin. Trypsin or plasmin treatment of PAPP-A resulted in the generation of a major 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 inaccessible to inactivation by soybean trypsin inhibitor and alpha 1-proteinase inhibitor. The mechanism of proteinase inhibition was likely to be entrapment, as described for alpha 2-macroglobulin.