Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases
✍ Scribed by Lawrence F. Kress
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 519 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Human plasma serine proteinase inhibitors (serpins) gradually lost activity when incubated with catalytic amounts of snake venom or bacterialmetalloproteinases. Electrophoretic analyses indicated that antithrombin 111, C l-inhibitor, and 012antiplasmin had been converted by limited proteolysis into modified species which retained inhibitory activity. Further proteolytic attack resulted in the formation of inactivated inhibitors; ocl-proteinase inhibitor (crl-antitrypsin) and cr,-antichymotrypsin were also enzymatically inactivated, but active intermediates were not detected. Sequence analyses indicated that the initial, noninactivating cleavage occurred in the amino-terminal region of the inhibitors. Inactivation resulted in all cases from the limited proteolysis of a single bond near, but not at, the reactive site bond in the carboxy-terminal region of the inhibitors. The results indicate that the serpins have two regions which are susceptible to limited proteolysis-one near the amino-terminal end and another in the exposed reactive site loop of the inhibitor.