[HTML][HTML] Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18

PC Guo, Z Dong, P Zhao, Y Zhang, H He, X Tan… - Scientific reports, 2015 - nature.com
PC Guo, Z Dong, P Zhao, Y Zhang, H He, X Tan, W Zhang, Q Xia
Scientific reports, 2015nature.com
Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait
to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori
at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that
the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably,
this inhibitiory reaction results from the formation of an intermediate complex, which then
follows for the digestion of protease and inhibitor into small fragments. This activity differs …
Abstract
Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development.
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