Proteinase inhibitor I1, Kazal <p>Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties. </p><p>This family of Kazal inhibitors, belongs to MEROPS inhibitor family I1, clan IA. They inhibit serine peptidases of the S1 family (<db_xref db="INTERPRO" dbkey="IPR001254"/>) [<cite idref="PUB00014133"/>]. The members are primarily metazoan, but includes exceptions in the alveolata (apicomplexa), stramenopiles, higher plants and bacteria.</p><p>Kazal inhibitors, which inhibit a number of serine proteases (such astrypsin and elastase), belong to family of proteins that includespancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor;and elastase inhibitor. These proteins contain between 1 and 7 Kazal-typeinhibitor repeats [<cite idref="PUB00003203"/>, <cite idref="PUB00000286"/>].</p> <p>The structure of the Kazal repeat includes a large quantity of extended chain, 2 short alpha-helices and a 3-stranded anti-parallel beta sheet [<cite idref="PUB00003203"/>].The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable [<cite idref="PUB00000286"/>]. Altering the enzyme-contact residues, and especially that of the active site bond, affects the the strength of inhibition and specificity of the inhibitor for particular serine proteases [<cite idref="PUB00000286"/>, <cite idref="PUB00000276"/>]. The presence of this Pfam domain is usually indicative of serine protease inhibitors, however, Kazal-like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors.</p>