Abstract
BACKGROUND: Trichinosis is one of the most widespread parasitic infections worldwide. Trichinella spiralis not only infects humans but can also utilize wild anddomestic animals as hosts. The serine protease inhibitors secreted by Trichinella spiralis play a critical role in its invasion and immune evasion. Serpins can effectively inhibit host proteases, although the host can mount a strongimmune response against to these inhibitors. RESULTS: In this study we analyzed the crystal structures of the serine protease inhibitors from Trichinella spiralis and Trichinella pseudospiralis, revealing that both serpins exhibit.structural characteristics typical of serine protease inhibitors. The similarity of both "breach" region and "shutter" region of the two serpins are very high, but the "hinge" region are different, the "hinge" of Tp-serpin is closed, while of Ts-serpin was partially inserted into sheet-A, suggesting that Tp-serpin had higher inhibition activity. Using alpha chymotrypsin as Ts-serpin and Tp-serpin protease targets, the two serpins enzyme inhibition activity were measured separately, by measuring the secondary inhibition rate constant, half inhibitory concentration IC50, inhibition of stoichiometric number parameters and confirmed both the serine protease inhibitory activity, and Tp-serpin slightly higher than that of Ts-serpin, but no inhibition activity of P1-P1' mutant. CONCLUSION: In this study, the mechanism of enzyme inhibition activity of serpin was studied by means of structural biology and biochemistry comprehensively. These discoveries provide a theoretical foundation for a deeper understanding of the inhibition mechanisms of serpins and for the development of new drugs and vaccines against Trichinella spiralis infection.