| Name | Inhibitor family I3 (Kunitz-P family) |
|---|
| Family type peptidase | I03.001 - soybean Kunitz trypsin inhibitor (Glycine max), MEROPS Accession MER0017895 (inhibitor unit: 25-205) |
| Content of family | Inhibitor family I3 contains inhibitors of serine and some other peptidases. |
| History |
Identifier created: MEROPS 6.1 (10 January 2003)
Members of both families I2 and I3 are known as Kunitz inhibitors, because Kunitz discovered the first members. However, the families are unrelated. To distinguish I2 and I3, the families are also known as the 'Kunitz-A' and 'Kunitz-P' families, because members are known from animals and plants, respectively. Kunitz first isolated soya bean trypsin inhibitor (I03.001) by crystallization (Kunitz, 1945). A few members of the family possess two reactive sites and are able to inhibit two peptidase molecules per inhibitor molecule; these are known as 'double-headed inhibitors'. |
| Peptidases inhibited | Peptidases inhibited mostly belong to family S1 (Laskowski & Kato, 1980), but subfamily I3A contains inhibitors of families A1 (Mares et al., 1989) and C1 (De Oliveira et al., 2001; Valueva et al., 1997; Franco et al., 2002). An inhibitor from potato (I03.002) inhibits cathepsin D (A01.009); an inhibitor from Bauhinia (I03.012) inhibits cruzipain (C01.075); and inhibitors from grasses (I03.004) inhibit subtilisin (S08.001) and alpha-amylase. Soya bean trypsin inhibitor inhibits not only trypsin (S01.151) but also chymotrypsin (S01.001), albeit much more weakly and at the same reactive site (Bosterling & Quast,1981). An inhibitor from Prosopis can inhibit trypsin and papain (C01.001) at the same reactive site (Franco et al., 2002). |
| Mechanism of inhibition | Members of family I3 inhibit serine peptidases by the Laskowski mechanism. |
| Molecular structure | The tertiary structure of the soya bean trypsin inhibitor in complex with pig trypsin was determined by Sweet et al., 1974. The inhibitor has an all beta structure with a closed beta barrel, and has a similar architecture to the non-peptidase, C-terminal domain of tentoxilysin (M27.001) and bontoxilysin (M27.002) of Clostridium. Most members of the family possess two disulfide bonds, Cys63-Cys110 and Cys160-Cys169 (see the Alignment); an exception is the inhibitor from Swartzia which has only the first of the two disulfide bridges (do Socorro et al., 2002). Soya bean trypsin inhibitor is synthesized with an N-terminal signal peptide and a C-terminal ten-residue extension. |
| Clan | IC |
| Biological functions | The biological functions of these inhibitors are unknown. They were assumed to help defend the plants from insect attack by interfering with the insect digestive system, but there is now evidence that insect pests can compensate for the inhibition (e.g. Brunelle et al., 2004). There are several genes for soya bean trypsin inhibitors which are expressed at different stages of the life cycle. The main inhibitor gene is expressed in the seed, where the inhibitor accumulates in the cotyledons, is not degraded during germination and is therefore not a storage protein (Jofuku et al., 1989). |
| Pharmaceutical and biotech relevance | Soya bean trypsin inhibitor has been identified as an inhalant antigen and a food allergen (Quirce et al., 2002). |
| Statistics for family I3 | Sequences: | 961 |
| Identifiers: | 33 |
| Identifiers with PDB entries: | 16 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Inhibitors and Homologues |
MEROPS ID |
Structure |
| soybean Kunitz trypsin inhibitor | I03.001 | Yes |
| cathepsin D inhibitor (Solanaceae) | I03.002 | - |
| alocasin | I03.003 | Yes |
| alpha-amylase/subtilisin inhibitor (Hordeum-type) | I03.004 | Yes |
| chymotrypsin inhibitor ECI (Erythrina variegata) | I03.005 | - |
| trypsin inhibitor (Enterolobium contortisiliquum) | I03.008 | - |
| winged-bean chymotrypsin inhibitor | I03.009 | Yes |
| trypsin inhibitor (Acacia confusa) | I03.010 | - |
| Erythrina-type trypsin/tissue plasminogen activator inhibitor | I03.011 | Yes |
| cruzipain inhibitor (Bauhinia bauhinioides) | I03.012 | Yes |
| sporamin | I03.013 | - |
| AtDr4 g.p. (Arabidopsis thaliana) | I03.015 | - |
| Bauhinia trypsin/plasma kallikrein inhibitor | I03.016 | Yes |
| Kunitz cysteine peptidase inhibitor 1 (plant) | I03.017 | - |
| trypsin inhibitor PtTI (Populus tremuloides and similar) | I03.018 | - |
| papain/trypsin inhibitor (Prosopis-type) | I03.019 | - |
| potato Kunitz-type trypsin inhibitor | I03.020 | Yes |
| Kunitz serine peptidase inhibitor (Delonix regia) | I03.021 | Yes |
| latex serine peptidase inhibitor (Papaya carica) | I03.022 | Yes |
| Leucaena-type trypsin inhibitor (Fabaceae) | I03.024 | Yes |
| Kunitz subtilisin inhibitor (Fabaceae-type) | I03.025 | Yes |
| chymotrypsin inhibitor (Schizolobium parahyba) | I03.026 | - |
| Bauhinia-type trypsin inhibitor | I03.027 | - |
| crucifer cysteine peptidase inhibitor | I03.028 | Yes |
| inhibitor AeTI (Archidendron ellipticum) | I03.029 | - |
| inhibitor MtTi2 (Medicago truncatulata) | I03.030 | Yes |
| AtKI1 (Arabidopsis thaliana) | I03.031 | - |
| factor Xa inhibitor BuXI ( Bauhinia sp.) | I03.032 | - |
| ILTI trypsin inhibitor (Inga laurina) | I03.033 | - |
| tamarind Kunitz trypsin inhibitor (Tamarindus indica) | I03.034 | Yes |
| Bauhinia-type elastase 2 inhibitor | I03.035 | - |
| Subfamily I3A non-peptidase homologues | non-peptidase homologue | - |
| Subfamily I3A unassigned peptidases | unassigned | Yes |
