Proteinase inhibitor I29, cathepsin propeptide <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 entry represents a peptidase inhibitor domain, which belongs to MEROPS peptidase inhibitor family I29. The domain is also found at the N terminus of a variety of peptidase precursors that belong to MEROPS peptidase subfamily C1A; these include cathepsin L, papain, and procaricain (<db_xref db="SWISSPROT" dbkey="P10056"/>) [<cite idref="PUB00022428"/>]. It forms an alpha-helical domain that runs through the substrate-binding site, preventing access. Removal of this region by proteolytic cleavage results in activation of the enzyme. This domain is also found, in one or more copies, in a variety of cysteine peptidase inhibitors such as salarin [<cite idref="PUB00028125"/>].</p>