Kunitztype

Kunitztype refers to a family of serine protease inhibitors that are defined by the presence of a Kunitz-type domain. The best known member is bovine pancreatic trypsin inhibitor (BPTI), a small, cysteine-rich protein described by Moses Kunitz in the mid-20th century. A typical Kunitz-type domain is about 50 to 60 amino acids in length and is stabilized by three disulfide bonds, giving it high stability in a variety of environments. Many proteins contain one or more Kunitz domains, and some are secreted enzymes or inhibitors as single-domain proteins while others are multi-domain.

The functional hallmark of Kunitz-type inhibitors is their ability to bind serine proteases in a substrate-like manner. They feature a reactive site loop that contains the P1 residue, which largely determines protease specificity. For trypsin inhibition, the P1 residue is commonly lysine or arginine. This loop inserts into the protease active site, blocking catalysis. Variation in the reactive loop among family members underlies broad or narrow protease specificity.

Distribution and significance are wide: Kunitz-type inhibitors are found in plants, animals, and some microorganisms. Plant inhibitors, such as soybean trypsin inhibitor, are important in defense against insect herbivores. In animals, tissue factor pathway inhibitor (TFPI) contains multiple Kunitz domains and contributes to regulation of coagulation. In addition to their biological roles, Kunitz-type domains are used in research and biotechnology as templates for designing protease inhibitors and for studying protein–protease interactions. The MEROPS database classifies these inhibitors as family I12.