In 2004 Rawlings and colleagues introduced a classification of protease inhibitors based on similarities detectable at the level of amino acid sequence.

[4] This classification initially identified 48 families of inhibitors that could be grouped into 26 related superfamily (or clans) by their structure.

Their mechanism of action relies on undergoing a large conformational change which inactivates their target's catalytic triad.

It seems likely that in both cases it is the C-terminus which becomes the active inhibitor after post-translational modifications of the full length, pre-peptide.

It is the ester linkages within the key, 12-residue region that circularise the molecule giving it its inhibitory conformation.

In the absence of saccharopepsin it is largely unstructured,[9] but in its presence, the inhibitor undergoes a conformational change forming an almost perfect alpha-helix from Asn2 to Met32 in the active site cleft of the peptidase.

The peptidase inhibitor family I36 domain is only found in a small number of proteins restricted to Streptomyces species.

It has 102 amino acid residues with two disulphide bridges and specifically inhibits metalloproteinases such as thermolysin, which belongs to MEROPS peptidase family M4.

[13] Chagasin has a beta-barrel structure, which is a unique variant of the immunoglobulin fold with homology to human CD8alpha.