Proteinase inhibitor I11, ecotin domain <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 proteinase inhibitors that belong to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from <taxon tax_id="562">Escherichia coli</taxon> and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1 (<db_xref db="INTERPRO" dbkey="IPR001254"/>) [<cite idref="PUB00014133"/>]. Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, <taxon tax_id="632">Yersinia pestis</taxon>, and <taxon tax_id="287">Pseudomonas aeruginosa</taxon>, all species that encounter the mammalian immune system inhibit neutrophil elastase strongly while ecotin from the plant pathogen <taxon tax_id="53336">Pantoea citrea</taxon> inhibits neutrophil elastase 1000-fold less than the others [<cite idref="PUB00014201"/>].</p> <p>They all potently inhibit pancreatic digestive peptidases trypsin and chymotrypsin, while showing more variable inhibition of the blood peptidases Factor Xa, thrombin, and urokinase-type plasminogen activator. </p><p>This entry represents the structural domain of ecotin, consisting of 8 beta strands organised in 2 sheets.</p>