Modification of the tandem reactive centres of human inter-alpha-trypsin inhibitor with butanedione and cis-dichlorodiammineplatinum(II).
Human inter-alpha-trypsin inhibitor (I alpha I) is a plasma proteinase inhibitor active against cathepsin G, leucocyte elastase, trypsin and chymotrypsin. It owes its broad inhibitory specificity to tandem Kunitz-type inhibitory domains within an N-terminal region. Sequence studies suggest that the reactive-centre residues critical for inhibition are methionine and arginine. Reaction of I alpha I with the arginine-modifying reagent butane-2,3-dione afforded partial loss of inhibitory activity against both cathepsin G and elastase but complete loss of activity against trypsin and chymotrypsin. Reaction of I alpha I with the methionine-modifying reagent cis-dichlorodiammineplatinum(II) resulted in partial loss of activity against cathepsin G and elastase but did not affect inhibition of either trypsin or chymotrypsin. Employment of both reagents eliminated inhibition of cathepsin G and elastase. These findings suggest that both cathepsin G and elastase are inhibited at either of the reactive centres of I alpha I. Trypsin and chymotrypsin, however, appear to be inhibited exclusively at the arginine reactive centre.
Swaim
M W
MW
Department of Pathology, Duke University Medical Centre, Durham, NC 27710.
Pizzo
S V
SV
D000510:Alpha-Globulins / Q000378:metabolism*; D000596:Amino Acids / Q000032:analysis; D001120:Arginine / Q000032:analysis; D001665:Binding Sites; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D002945:Cisplatin / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D008715:Methionine / Q000032:analysis; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D014361:Trypsin Inhibitors / Q000378:metabolism*
D000510:Alpha-Globulins; D000596:Amino Acids; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D014361:Trypsin Inhibitors; C011877:inter-alpha-inhibitor; C007366:diepoxybutane; D001120:Arginine; D008715:Methionine; D002403:Cathepsins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D002945:Cisplatin