Protease inhibitors proteins

Proteases are regulated in vivo by autoinhibition (as zymogens), proteolytic activation, turnover and by endogenous protease inhibitor proteins. The following brief sketch of protease complexity is accompanied by succinct reference to the physiological context and hence the potential pharmacological relevance of plant-derived protease inhibitors to be described later in this review. 

While a few very potent non-peptide protease inhibitors (Pis) have been isolated from plants many plant protease inhibitor proteins (PIPs) have evolved to have protease interaction Kj values in the nanomolar and picomolar range. These extraordinary affinities derive from the matching of the PI protein amino sequence about the scissile peptide bond (Pl-Pl ) and evolution of adjacent sequences to fit and interact appropriately within the target protease active site [1, 120, 121]. The structure and function of the different classes of PI proteins from plants are succinctly but comprehensively reviewed below. 

A variety of aspartic protease inhibitor (API) proteins have been resolved from plants [122-135] of which the best characterized at the gene and protein level are those from Solanum tuberosum (potato) (Solanaceae) [124-134] (Table 4). The potato aspartic protease inhibitor proteins are typically about 190 residues (about 20 kDa), have 3 disulphide bridges, are homologous to the soybean trypsin inhibitor (Kunitz) family Pis [133] and can also inhibit trypsin [124-134] (Table 4). 

Table 4. Plant aspartic protease inhibitor proteins...

The number of amino acid residues (aa), cysteines (Cys) and disulphide bonds (S-S) is given together with molecular mass (Da) and the scissile bond amino acid sequence at the the reactive site of the protease inhibitor protein (Pl-Pl, the one letter amino acid code being employed). 

Plant species (other name) (Family) Protease inhibitor protein Protease specificity (IC50) TKd, Ki1 (reactive site) Ref. 

Cysteine protease inhibitor proteins from plants... 

Arabidopsis thaliana (mouse-ear cress) (Brassicaceae) Cysteine protease inhibitor (CPI) protein homologues (genes) (11-51 kDa proproteins) Cysteine protease inhibitor protein homologues [141- 146]... 

Legume (Fabaceae) Bowman-Birk protease inhibitor proteins (BBPIPs) are typically double-headed protease inhibitors with 14 cysteines (i.e. 7 S-S links) and molecular masses of 7-9 kDa. All the BBPIPs listed were isolated from seeds except for the Medicago sativa (alfalfa) leaf BBPIPs. For other details see the legend to Table 4. 

This review has succinctly summarized what is presently known of nonprotein and protein protease inhibitors from plants. The affinities of the non-protein inhibitors for particular proteases are generally much lower than those of plant protease inhibitor proteins (PIPs). Nevertheless the non-protein protease inhibitors may provide structure/activity starting points for development of pharmaceutically useful compounds of much higher affinity. The plant PIP literature has been comprehensively surveyed in this review. However electronic databases such as EMBL and SWISSPROT contain further accessible plant PIP sequences [581]. The array of potent plant PIPs reflects the co-evolution of plant defensive proteins and insect resistance [582]. Potent, stable, protease inhibitor proteins have potential transgenic crop agriculture applications as well as potential chemotherapeutic applications. 

Angiotensin I converting enzyme Acquired immunodeficiency syndrome Aspartic protease inhibitor Bowman Birk protease inhibitor protein Chymotrypsin Cysteine protease inhibitor Endothelin-converting enzyme Elastase... 

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