STISoybean trypsin inhibitor (Kunitz) family of protease inhibitors
|SMART accession number:||SM00452|
|Interpro abstract (IPR002160):|
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.
The Kunitz-type soybean trypsin inhibitor (STI) family consists mainly of proteinase inhibitors from Leguminosae seeds [(PUBMED:14705960)]. They belong to MEROPS inhibitor family I3, clan IC. They exhibit proteinase inhibitory activity against serine proteinases; trypsin (MEROPS peptidase family S1, IPR001254) and subtilisin (MEROPS peptidase family S8, IPR000209), thiol proteinases (MEROPS peptidase family C1, IPR000668) and aspartic proteinases (MEROPS peptidase family A1, IPR001461) [(PUBMED:14705960)].
Inhibitors from cereals are active against subtilisin and endogenous alpha-amylases, while some also inhibit tissue plasminogen activator. The inhibitors are usually specific for either trypsin or chymotrypsin, and some are effective against both. They are thought to protect the seeds against consumption by animal predators, while at the same time existing as seed storage proteins themselves - all the actively inhibitory members contain 2 disulphide bridges. The existence of a member with no inhibitory activity, winged bean albumin 1, suggests that the inhibitors may have evolved from seed storage proteins.
Proteins from the Kunitz family contain from 170 to 200 amino acid residues and one or two intra-chain disulphide bonds. The best conserved region is found in their N-terminal section. The crystal structures of soybean trypsin inhibitor (STI), trypsin inhibitor DE-3 from the Kaffir tree Erythrina caffra (ETI) [(PUBMED:1988676)] and the bifunctional proteinase K/alpha-amylase inhibitor from wheat (PK13) have been solved, showing them to share the same 12-stranded beta-sheet structure as those of interleukin-1 and heparin-binding growth factors [(PUBMED:1738162)]. The beta-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel beta-barrel. Despite the structural similarity, STI shows no interleukin-1 bioactivity, presumably as a result of their primary sequence disparities. The active inhibitory site containing the scissile bond is located in the loop between beta-strands 4 and 5 in STI and ETI.
The STIs belong to a superfamily that also contains the interleukin-1 proteins, heparin binding growth factors (HBGF) and histactophilin, all of which have very similar structures, but share no sequence similarity with the STI family.
|GO function:||endopeptidase inhibitor activity (GO:0004866)|
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