Accession number: PF00050
Kazal-type serine protease inhibitor domain
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 protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides. Alignment also includes a single domain from transporters in the OATP/PGT family P46721. |
Description
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. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen.
This family of Kazal inhibitors, belongs to MEROPS inhibitor family I1, clan IA. They inhibit serine peptidases of the S1 family () PUBMED:14705960. The members are primarily metazoan, but includes exceptions in the alveolata (apicomplexa), stramenopiles, higher plants and bacteria.
Kazal inhibitors, which inhibit a number of serine proteases (such as
trypsin and elastase), belong to family of proteins that includes
pancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor;
and elastase inhibitor. These proteins contain between 1 and 7 Kazal-type
inhibitor repeats PUBMED:6699915, PUBMED:3828298. 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 PUBMED:6699915.The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable PUBMED:3828298. 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 PUBMED:3828298, PUBMED:7046785. 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.
Description text from InterPro entry IPR002350
|
