InterPro domain: IPR000877

This family of eukaryotic proteinase inhibitors, belongs to MEROPS inhibitor family I12, clan IF. They predominantly inhibit serine peptidases of the S1 family ( IPR001254 ) [ 1 ]. They play a role in defense response against pathogens and insects, but they also have been studied as therapeutic treatment in cancer and inflammatory disorders [ 2 ]. Exceptionally, cowpea trypsin inhibitor inhibits a cathepsin L-like cysteine proteinase CPL-1 from the nematode Heterodera glycines [ 3 ].

The Bowman-Birk inhibitor family [ 4 , 4 ] is one of the numerous families of serine proteinase inhibitors. They have a duplicated structure and generally possess two distinct inhibitory sites. These inhibitors are primarily found in plants and in particular in the seeds of legumes as well as in cereal grains. In cereals they exist in two forms, one of which is a duplication of the basic structure [ 5 ]. Proteins of the Bowman-Birk inhibitor family of serine proteinase inhibitors interact with the enzymes they inhibit via an exposed surface loop that adopts the canonical proteinase inhibitory conformation. The resulting non-covalent complex renders the proteinase inactive. This inhibition mechanism is common for the majority of serine proteinase inhibitor proteins and many analogous examples are known. A particular feature of the Bowman-Birk inhibitor protein, however, is that the interacting loop is a particularly well-defined disulphide-linked short beta-sheet region [ 6 , 7 , 8 ].

1. Evolutionary families of peptidase inhibitors. Biochem. J. 378, 705-16
2. Isolation and functional diversity of Bowman-Birk type serine proteinase inhibitors from Hyacinthus orientalis. Biochem J 478, 1287-1301
3. Characterization of intestinally active proteinases of cyst-nematodes. Parasitology 113 ( Pt 4), 415-24
4. Protein inhibitors of proteinases. Annu. Rev. Biochem. 49, 593-626
5. The complete amino acid sequence of rice bran trypsin inhibitor. J. Biochem. 102, 297-306
6. Synthetic peptide mimics of the Bowman-Birk inhibitor protein. Curr. Med. Chem. 8, 909-17
7. Peptide mimics of the Bowman-Birk inhibitor reactive site loop. Biopolymers 66, 79-92
8. The structural basis of a conserved P2 threonine in canonical serine proteinase inhibitors. J. Biomol. Struct. Dyn. 20, 645-56