Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases

1986 ◽  
Vol 32 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Lawrence F. Kress
Keyword(s):  
Human Plasma ◽  
Snake Venom ◽  
Proteinase Inhibitors ◽  
Limited Proteolysis ◽  
Serine Proteinase ◽  
Reactive Site ◽  
Serine Proteinase Inhibitors

scholarly journals Isolation and functional diversity of Bowman-Birk type serine proteinase inhibitors from Hyacinthus orientalis

2021 ◽  
Author(s):  
Narumi Aoki-Shioi ◽  
Shigeyuki Terada ◽  
Roland Hellinger ◽  
Yoshitaka Furuta ◽  
Christian W Gruber
Keyword(s):  
Inhibitory Activity ◽  
Rational Design ◽  
Mutational Analysis ◽  
Proteinase Inhibitors ◽  
Serine Proteinase ◽  
Reactive Site ◽  
Serine Proteinase Inhibitors ◽  
Linker Sequence ◽  
Representative Model ◽  
Hyacinthus Orientalis

Bowman–Birk inhibitors (BBI) are plant-derived serine proteinase inhibitors. Endogenously, they function as defense molecules against pathogens and insects, but they also have been explored for applications in cancer treatment and inflammatory disorders. Here, we isolated 15 novel BBIs from the bulb of Hyacinthus orientalis (termed HOSPIs). These isoinhibitors consisted of two or three chains, respectively, that are linked by disulfides bonds based on proposed cleavage sites in the canonical BBI reactive site loop. They strongly inhibited trypsin (Ki = 0.22 - 167 nM) and α-chymotrypsin (Ki = 19 - 1200 nM). Notably, HOSPI-B4 contains a six-residue reactive loop, which appears to be the smallest such motif discovered in BBIs to date. HOSPI-A6 and -A7 contain an unusual reactive site, i.e. Leu-Met at the P1-P1' position and have strong inhibitory activity against trypsin, α-chymotrypsin and elastase. Analysis of the cDNA encoding HOSPIs revealed that the precursors have HOSPI-like domains repeated at least twice with a defined linker sequence connecting individual domains. Lastly, mutational analysis of HOSPIs suggested that the linker sequence does not affect the inhibitory activity, and a Thr residue at the P2 site and a Pro at the P3' site are crucial for elastase inhibition. Using mammalian proteases as representative model system, we gain novel insight into the sequence diversity and proteolytic activity of plant BBI. These results may aid the rational design of BBI peptides with potent and distinct inhibitory activity against human, pathogen, or insect serine proteinases.

Boophilus microplus tick larvae, a rich source of Kunitz type serine proteinase inhibitors

Biochimie ◽  
2004 ◽  
Vol 86 (9-10) ◽  
pp. 643-649 ◽  
Author(s):  
Sergio Daishi Sasaki ◽  
Simone Sant’Anna Azzolini ◽  
Izaura Yoshico Hirata ◽  
Renato Andreotti ◽  
Aparecida Sadae Tanaka
Keyword(s):  
Proteinase Inhibitors ◽  
Serine Proteinase ◽  
Boophilus Microplus ◽  
Rich Source ◽  
Serine Proteinase Inhibitors ◽  
Kunitz Type
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