title: Elastase inhibition by the inter-alpha-trypsin inhibitor and derived inhibitors of man and cattle.
abstract: The inhibitory properties of HI-14 and BI-14, the active 14-kDa parts released from the corresponding human and bovine inter-alpha-trypsin inhibitors, are compared. The structurally homologous inhibitors composed of two 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, whereas 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 from this enzyme. Human ITI 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.
mesh_terms: D000510:Alpha-Globulins / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology; D009928:Organ Specificity; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D014361:Trypsin Inhibitors / Q000494:pharmacology*
chemical_list: D000510:Alpha-Globulins; D014361:Trypsin Inhibitors; C011877:inter-alpha-inhibitor; D002918:Chymotrypsin; D010196:Pancreatic Elastase