Elastase Inhibition by the Inter-α-Trypsin Inhibitor and Derived Inhibitors of Man and Cattle

Abstract
The inhibitory properties of HI-14 and BI-14, the active 14-kDa [kilodalton] parts released from the corresponding human and bovine inter-.alpha.-trypsin inhibitors, are compared. The structurally homologous inhibitors composed of 2 tandem Kunitz-type domains differ in their inhibitory specificity, although the reactive site residue in position P1 is occupied by identical (arginine in the C-terminal domain II) or similar (methionine and leucine in the N-terminal domain I of HI-14 and BI-14, respectively) amino acid residues. The N-terminal domain I of HI-14 is completely inactive against chymotrypsin and pancreatic elastase; BI-14 is a strong inhibitor of these enzymes. Elastase from polymorphonuclear granulocytes interacts with both inhibitors but with different affinities. Compared with the bovine inhibitor, the human inhibitor shows a much lower affinity for this enzyme. Human ITI [inter-.alpha.-trypsin inhibitor] and its physiological 30-kDa derivative (HI-30) show the same inhibitory properties as HI-14. The differences between human and bovine inhibitors might be explained by a preceding oxidation of Met in vivo of the reactive site residue in position P1 and/or by the influence of the environmental parts connected with this antielastase reactive site region in human ITI or in the active domains thereof.

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