Kunitz-type soybean trypsin inhibitors

I Soybean trypsin inhibitor (Kunitz-type) PF00197... 

The Bowman-Birk type protease inhibitors represent a class of low molecular weight, cysteine-rich proteins found in legume seeds (.10). The major Bowman-Birk inhibitor in soybean seeds is a double-headed protein capable of blocking the activity of both trypsin and chymotrypsin. This protein represents approximately 4% of the total protein in soybean seeds (1J ). In contrast to the soybean trypsin inhibitor (Kunitz), the "double-headed inhibitor (referred to as BB) is typical of protease inhibitors present in a large number of legume seeds for example, peanuts (12) chick peas (33)5 kidney beans (3JO adzuki beans (33) lima beans (16). 

Solanum (potato) Kunitz PEPs inhibit the aspartic protease cathepsin D as well as trypsin [125-134] and potato cysteine protease inhibitor (PCPI) inhibits a variety of cysteine proteases [185-188]. The crystal structures of soybean trypsin inhibitor (STI) [362, 368] and of Erythrina trypsin inhibitor (ETI) [350] have been determined. The structure of this type of plant Kunitz serine PIP involves a [3-barrel formed by 6 loop-linked antiparallel [3-strands with a lid formed by 6 further loop-linked antiparallel [3-strands. The scissile bond is located within a loop that extends out from the surface of the [3-barrel [350, 362, 368]. 

Figure 3 Complex formation between trypsin and soybean trypsin inhibitor exemplifies the mechanism of Kunitz-type inhibitors (PDB 1AVW). Greatly reduced peptide bond hydrolysis rates lead to inhibition.

Figure 4, Kinin generating cascade and various vascular mediators in cancer tissues affecting the EPR effect. Mediators, enzymes, and inhibitors are shown. See text for details. M, macrophage PMN, polymorphoneuclear cells COXs, cyclooxygenases PCs, prostaglandins. SBTl, soybean trypsin inhibitor (Kunitz type) ONOO", peroxynitrite NO, nitric oxid MMP, matrix metalloproteinases.

Troncoso, M.E V.A. Biron SA. Longhi LA. Retegui C. Wolfenstein-Todel. Peltophorum dubium and soybean Kunitz-type trypsin inhibitors induce human Jurkat cell apoptosis. Int. 

Protease inhibitors in soybeans, known as trypsin inhibitors (TIs), play important roles in nutritional properties of soybeans and soy protein products. Two types of TI are the Kunitz inhibitor and the Bowman-Birk inhibitor. The Kunitz inhibitor has a MW of 21,500 with two disulfide bonds, while the Bowman-Birk inhibitor has a MW of 7,900 with seven disulfide bonds (Wolf, 1977). The large ratio of disulfide bonds to MW in the Bowman-Birk inhibitor stabilizes protein conformation and makes the Bowman-Birk inhibitor highly resistant to heat denaturation and inactivation. The Kunitz inhibitor inhibits trypsin, while the Bowman-Birk inhibitor inhibits both trypsin and chymotrypsin. The kinetics of TI inactivation when heating at high water activity were determined by Johnson et al. (1980) they estimated that 83-91% of the TI activity in soybeans is due to the Kunitz inhibitor. Recently, the Bowman-Birk inhibitor was attributed cancer-protecting qualities and also interest exists in using purified soy TI to treat AIDS patients (Kennedy, 1995, 1998 Kennedy Szuhaj, 1994). 

Snail epidermis contains at least six trypsin-kallikrein inhibitors with molecular weights ranging from 6431 to 6591 (70-72). The soybean contains two basic types of protease inhibitors, the Kunitz inhibitor of 21,500 daltons (73) and the Bowman-Birk inhibitor of 7975 daltons (74). The two are quite different proteins as shown in Figure 6. The Great Northern bean (Phaseolus vulgaris) has at least three trypsin isoinhibitors ranging in molecular weight from 8086 to 8884 (15). There are four and possibly six isoinhibitors of trypsin in lima bean (Phaseolus lunatus)(75). 

Plasmin, fibrinolysin, a serine protease catalyzing Lys-Xaa and Arg-Xaa bond cleavage similar to that of trypsin. Plasmin is the key protease in blood clot lysis, and its major natural substrates are fibrinogen and fibrin. Human plasmin is derived from plasminogen, and is a two-chain protein consisting of the A or H chain (Mr 65 kDa) and the B or L chain (Mr 27.7 kDa). The active site is located in the B chain. The various molecular forms of plasmin are inactivated by protein inhibitors such as the Kunitz type, serpins, soybean and limabean trypsin inhibitors. The most important, fast-acting inhibitor of plasmin... 

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