Sabellastarte magnifica Carboxypetidase Inhibitor: the first Kunitz inhibitor simultaneously interacting with carboxypeptidases and serine proteases.

Sabellastarte magnifica Carboxypetidase Inhibitor: the first Kunitz inhibitor simultaneously interacting with carboxypeptidases and serine proteases. Biochimie. 2018 May 03;: Authors: Reytor González ML, Alonso-Del-Rivero Antigua M, Hedstrom L, Kuzmič P, Pires JR Abstract Multi-domain inhibitors capable to block the activity of different classes of proteases are not very common in nature. However, these kinds of molecules are attractive systems for biomedical or biotechnological applications, where two or more different targets need to be neutralized. SmCI, the Sabellastarte magnifica Carboxypeptidase Inhibitor, is a tri-domain BPTI-Kunitz inhibitor capable to inhibit serine proteases and A-like metallocarboxypeptidases. The BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases. SmCI is therefore, the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. The X-ray structure of the SmCI-carboxypeptidase A complex previously obtained by us, revealed that this enzyme interacts with SmCI N-tail. In the complex, the reactive loops for serine protease inhibition remain fully exposed to the solvent in each domain, suggesting SmCI can simultaneously interact with multiple serine proteases. The twofold goals of this study were: i) to establish serine proteases-SmCI binding stoichiometry, given that the inhibitor is comprised of three potential binding domains; and ii) to...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research