Protease inhibitors
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The first known Knottins
were protease inhibitors
Inhibitors with the knottin scaffold have been isolated from plants.
Insects and phytopathogenic microorganisms secrete enzymes causing
proteolytic digestion or proteins. It is likely that, to defend themselves
from these attacks,
plants have developped expression of proteinase inhibitors.
[Habib & Fazili, 2007]
- Cyclotide psysol 2:
inhibitor of human prolyl oligopeptidase (POP)
[Hellinger et al., 2015].
- Roseltide:
a knottin-type neutrophil elastase inhibitor derived from Hibiscus sabdariffa
[Loo et al., 2016].
- PCI: The potato
carboxypeptidase A inhibitor PCI inhibits its cognate enzyme
through its C-terminus [Rees
& Lipscomb, 1982].
- Squash:
The serine protease inhibitors of the "squash"
family inhibit their cognate enzyme through a canonical loop
located between Cys1 and Cys2 [Bode
et al., 1989].
- α-Amylase:
The α-amylase inhibitor from Amaranth AAI, inhibits α-amylase
from insects using a new mode of action. The interaction surface
includes two segments: (i) the loop between Cys1 and Cys2 and
(ii) the last strand of the β-hairpin [Pereira
et al., 1999].
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