Swaim M W, Pizzo S V
Department of Pathology, Duke University Medical Centre, Durham, NC 27710.
Biochem J. 1988 Aug 15;254(1):171-8. doi: 10.1042/bj2540171.
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.
人α-间胰蛋白酶抑制剂（IαI）是一种血浆蛋白酶抑制剂，对组织蛋白酶G、白细胞弹性蛋白酶、胰蛋白酶和糜蛋白酶具有活性。它广泛的抑制特异性归因于N端区域内串联的Kunitz型抑制结构域。序列研究表明，对抑制至关重要的反应中心残基是甲硫氨酸和精氨酸。IαI与精氨酸修饰试剂丁二酮-2,3-二酮反应，导致对组织蛋白酶G和弹性蛋白酶的抑制活性部分丧失，但对胰蛋白酶和糜蛋白酶的活性完全丧失。IαI与甲硫氨酸修饰试剂顺式二氯二氨合铂（II）反应，导致对组织蛋白酶G和弹性蛋白酶的活性部分丧失，但不影响对胰蛋白酶或糜蛋白酶的抑制。使用这两种试剂均可消除对组织蛋白酶G和弹性蛋白酶的抑制。这些发现表明，组织蛋白酶G和弹性蛋白酶在IαI的任何一个反应中心均受到抑制。然而，胰蛋白酶和糜蛋白酶似乎仅在精氨酸反应中心受到抑制。
