C1 Inhibitor (C1 INH)

C1 inhibitor (C1 INH), a member of the serpin family of protease inhibitors, has a similar structure and mechanism of protease inactivation to other members of the family. For protease inactivation, the protease recognizes the reactive center loop of serpins, which is displayed above the surface of the molecule. Cleavage of the peptide bond (P1-P1’) at the reactive center induces a molecular rearrangement and leads to covalent bond generation between the P1 residue of the inhibitor and the active site serine of the protease. C1 INH inactivates many proteases such as contact system proteases (factor XII, plasma kallikrein), the fibrinolytic proteases (plasmin, tissue plasminogen activator), complement system proteases (C1r, C1s, MASP2), and an intrinsic coagulation protease (factor XI).

Indeed, the major activity of C1 INH is protease inhibition. Nevertheless, a variety of studies have described the non-covalent interaction of C1 inhibitor with many other substances, including the complement component C3, gram-negative endotoxin, extracellular matrix components, endothelial cells, and leukocytes, as well as several infectious agents. It has proven that these interactions do not seem to depend upon protease inhibitor function, at least in some cases, to have potentially essential functional consequences.

Fig.1 Interaction of C1INH with plasmatic cascades. (Panagiotou, 2018)

Reference

1. Panagiotou, A., et al. The lectin pathway of complement in myocardial ischemia/reperfusion injury—review of its significance and the potential impact of therapeutic interference by C1 esterase inhibitor. Frontiers in immunology. 2018, 9, 1151.