InterPro domain: IPR036058

Canonical serine proteinase inhibitors are distributed in a wide range of organisms from all kingdoms of life and play crucial role in various physiological mechanisms [ 1 ]. They interact from the canonical proteinase-inhibitor binding loop, where P1 residue has a predominant role (the residue at the P1 position contributing the carbonyl portion to the reactive-site peptide bond). These so-called canonical inhibitors bind to their cognate enzymes in the same manner as a good substrate, but are cleaved extremely slowly. Kazal-type inhibitors represent the most studied canonical proteinase inhibitors. Kazal inhibitors are extremely variable at their reactive sites. However, some regularity prevails such as the presence of lysine at position P1 indicating strong inhibition of trypsin [ 2 ].

The Kazal inhibitor has six cysteine residues engaged in disulfide bonds arranged as shown in the following schematic representation:

 +------------------+ | | *******************|*** xxxxxxxxCxxxxxxCx#xxxxxCxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxC | | | | | +-------------|-----------------+ +----------------------------+'C': conserved cysteine involved in a disulfide bond.'#': active site residue.'*': position of the pattern.

The structure of classical Kazal domains consists of a central alpha helix, which is inserted between two beta-strands and a third that is toward the C terminus [ 3 ]. The reactive site P1 and the conformation of the reactive site loop is structurally highly conserved, similar to the canonical conformation of small serine proteinase inhibitors.

This entry represents the Kazal domain superfamily.

1. Protein inhibitors of proteinases. Annu. Rev. Biochem. 49, 593-626
2. What can the structures of enzyme-inhibitor complexes tell us about the structures of enzyme substrate complexes? Biochim. Biophys. Acta 1477, 324-37
3. Crystallographic refinement of Japanese quail ovomucoid, a Kazal-type inhibitor, and model building studies of complexes with serine proteases. J. Mol. Biol. 158, 515-37