Protease inhibitors squash family

Based on their sequence homology, disulfide connectivity, and cysteine location within the sequence and chemistry of the reactive site. Pis can be assigned to distinct families, as classified by Laskowski and Kato. Kunitz-type, Bowman—Birk-type, Potato type I and type II, and squash inhibitors are members of these families shown in Table 3. For inhibitors not falling into these classifications more families have been proposed. Pis can also be classified by their target/mode of action. Plants have been found to express Pis that target serine proteinases, cysteine proteinases, aspartic proteinases, and metallo-proteinases. Serine and cysteine protease inhibitors are the best-studied PIs. ... 

Vietnamese squash) which are cyclic peptides (cyclotides) [541]. The small size, exceptional stability and protease inhibitor potency of these cyclic squash family PIPs make them potentially very useful lead compounds and structural scaffolds for pharmaceutical development [541], The structures of various squash family PIPs have been determined, namely those of Cucurbita maxima CMTI-I [544, 545], Cucurbita pepo CPTI-n [545], Momordica charantia MCTI-A [556, 557] and the cyclotide Momordica cochinchinensis McoTI-U [541]. The linear squash PIP structures involve anti-parallel P-strand elements beneath a loop which contains the protease binding site [544, 545, 556, 557]. 

Table 17. Squash family serine protease inhibitors...

The squash family serine protease inhibitors all have molecular masses of about 3 kDa and have 6 cysteines (i.e. 3 disulphide links). For other details see the legend to Table 4. 

Some of these Pis are among the most potent naturally occurring enzyme inhibitors or protein ligands. Thus the squash family serine Pis have protease K values of the order of... 

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