third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains
This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), Bombyx mori cocoon shell-associated trypsin inhibitor (CSTI), Bombus terrestris Kunitz-type serine protease inhibitor Bt-KTI, and similar domains. SmCI is a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. CSTI and Bt-KTI are single Kunitz domain proteins that inhibit trypsin; in addition, Bt-KTI also inhibits plasmin. This model contains the third Kunitz domain of SmCI which has a structure similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.
Jiyao W et al.(2023). "The conserved domain database in 2023.",