Table serpins

The sensitivity of many serine-protease inhibitors (serpins) to ROIs has been determined in a number of groups and is summarized in Table 2. Of these serine-protease inhibitors, the most sensitive to inactivation by oxidants like OC1- or chloramines are those which contain methionine at or juxtaposed to the reactive centre [49] (e.g. plasminogen activator-inhibitor-1 (PAI-1), oq-proteinase inhibitor and 0(2-antiplasmin). Inactivation is thought to principally be due to the oxidation of these methionine residues to methionine sulfoxide [50-52]. PAI-1, which is rapidly inactivated in plasma, is also extremely sensitive to oxidants like iV-chlorosuccinimide, chloramine-T and H2O2, through a reaction involving oxidation of the reactive-site methionine. 

If thrombin and factor Xa, the major activated blood coagulation factors (Fig. 11.6), escape into healthy blood vessels, blood clots will develop and occlude capillaries throughout the body. Direct inhibition of these activated enzymes in the blood flow utilizes serine protease inhibitors, of which there are two common types a Kunitz inhibitor and a serpin. The former possess a Kunitz domain, a convex antiparallel (1-sheet that exactly fits into the concave active site of a serine protease, directly blocking it (lock and key mechanism). By contrast, serpins undergo complex interactions with other proteins to cause conformational changes that bait and block the catalytic action (Fig. 11.12 shows the bait). Table 11.3 fists the major coagulation inhibitors and cofactors, their targets and mechanisms of action. 

Table 1. Viral anti-inflammatory serpins assessed for anti-inflammatory activity in preclinical animal models...

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