Bowman-Birk

Some of the best investigated anti-nutrients are the enzyme inhibitors present in legumes and other plants. The Bowman-Birk and the Kunitz inhibitors of trypsin and other proteases are among the best characterized. In contrast to the non-specific and widespread influences of tannins and lectins (Carmona, 1996), the Bowman-Birk, Kunitz and other such inhibitors target specific enzymes. Corresponding with this, proteases and other digestive enzymes vary in sensitivity to the different inhibitors. 

A different approach toward cyclic peptides has been presented by Leatherbarrow and coworkers, employing ring-dosing metathesis (RCM) on a solid support [50], The authors reported on the synthesis of conformationally strained cyclic peptides of the Bowman-Birk inhibitor type, which are naturally occurring serine protease... 

BowB Bowman-Birk type proteinase inhibitor E(P) 0(0) 0(0) 1SBW... 

Inhibition of trypsin is another mechanism of activity recently discovered in plant defensins. CfDl and CfD2 from Cassia fistula were the first plant defensins to be identified as trypsin inhibitors. Cp-thionin from cowpea was more recently discovered to have inhibitory potency against trypsin. Searches of protein sequence databases have yielded a number of other plant proteins annotated as trypsin inhibitors or potential trypsin inhibitors. These annotations were most likely made on the basis of sequence similarities with other known trypsin inhibitors, namely the Bowman—Birk trypsin inhibitor. Since the actual framework of the disulfide bonds is not known, it is possible that structure and therefore activity differ from this prototype framework. ... 

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. ... 

Bowman-Birk protease inhibitors (BBIs) are among the best-studied serine protease inhibitors. They are found abundantly in dicotyledonous and monocotyledonous plants, with the former species expressing inhibitors of approximately 8 kDa in size with two reactive sites (double headed) and the latter expressing 8 kDa inhibitors with one reactive site and 16 kDa inhibitors with two reactive sites. Dicot BBIs feature 14 cysteine residues involved in disulfide bonds monocot BBIs have 10 cysteine residues. ... 

II Soybean trypsin inhibitor (Bowman-Birk-type) PF00228... 

Figure 10 The global structures of Bowman-Birk inhibitors are diverse, but the reactive sites are structurally highly conserved. Reactive sites are oriented to the bottom right corner. The double-stranded /3-sheets neighboring the reactive sites are clearly visible, (a) 1 mvz, (b) 1 bbi, and (c) 1 h34. (d) The overlay of the backbone traces of the three BBIs ((a)-(c), colors as before) reveals their structural similarity. Additionally SFTI-1 (green, Ijbl) adopts the same fold in its active site. The residues (Arg in 1 mvz, Lys for other peptides) are also shown N and C denote the N- and C-termini of the truncated loops.

Potl inhibitors differ from other protease inhibitors, and from all other defense peptides mentioned thus far, in their relative lack of disulfide bonds. This means that the loop with the reactive site is not fixed, as it is in the Bowman-Birk inhibitors, yet they still form a stable fold, as shown in Figure 11. An interesting feature of some Potl inhibitors is their tendency to form stable, noncovalently bound oligomers. This has, for example, been shown for chymotrypsin inhibitor I from tomato. This peptide has a monomer weight of 8300 Da under dissociating sodium dodecyl sulfate (SDS) gel conditions. Gel filtration and ultracentrifugal analysis revealed a... 

Chen, R, et al. (1992). Reactive sites of an anticarcinogenic Bowman-Birk proteinase inhibitor are similar to other trypsin inhibitors. /. Biol. Chem. 267,1990-1994. 

Krishna Murthy, H. M., et al. (1999). Crystallization, characterization and measurement of MAD data on crystals of dengue virus NS3 serine protease complexed with mung-bean Bowman-Birk inhibitor. Acta Crystallogr D 55,1370-1372. 

Murthy, H. M., et al. (2000). Crystal structure of Dengue virus NS3 protease in complex with a Bowman-Birk inhibitor implications for flaviviral polyprotein processing and drug design. /. Mol. Biol. 301, 759-767. 

NT028 Witschi, H., and I. Espiritu. Development of tobacco smoke-induced lung tumors in mice fed Bowman-Birk protease inhibitor concentrate (BBIC). Cancer Lett 2002 183(2) 141-146. 

Baturay. N. Kennedy, A.R. (1986) Pyrene acts as a cocarcinogen with the carcinogens benzo[o]pyrene, P-propiolactone and radiation in the induction of malignant transformation in cultured mouse fibroblasts soybean extract containing the Bowman-Birk inhibitor acts as an anticarcinogen. Cell Biol. Toxicol., 2, 21-32... 

Among the EST database of ragi sequences, there are two groups of bifunctional proteinase inhibitor trypsin a-amylase from seeds of ragi sequences. The upper clade was further subdivided (Fig. 6.10). Wang et al. (2008) concluded that there was great diversity in the sequence of different Bowman-Birk inhibitors in emmer wheat both within and between populations. 

FIGURE 6.10 Divergences in sequence of some ragi EST clones from that of an authentic Bowman Birk inhibitor (gi 94959241) using the Maximum Composite Likelihood Pairwise distance calculation and Mega4 (Tamura et al., 2007). 

Chymotrypsin (3.4.21.1) Avazyme, Chyrnar, Enzeon, Quimar Calcium (3-Phenylpropionate [26], aprotinin [5,44,45,141-144], Bowman-Birk inhibitor [7,141,145], benzyloxycarbonyl-Pro-Phe-CHO [43], chicken ovoinhibitor [47], chymostatin [3,141], DFP [26], FK-448 [3], PMSF [26], polycarbophil-cysteine [67], soybean trypsin inhibitor [5,7,51], sugar biphenylboronic acids complexes [146], poly(acrylate) derivatives [49]... 

Aprotinin is a polypeptide consisting of 58 amino acid residues derived from bovine lung tissues and shows inhibitory activity toward various proteolytic enzymes including chymo-trypsin, kallikrein, plasmin, and trypsin. It was also one of the first enzyme inhibitors used as an auxiliary agent for oral (poly)peptide administration. The co-administration of aprotinin led to an increased bioavailability of peptide and protein drugs [5,44,45], The Bowman-Birk inhibitor (71 amino acids, 8 kDa) and the Kunitz trypsin inhibitor (184 amino acids, 21 kDa) belong to the soybean trypsin inhibitors. Both are known to inhibit trypsin, chymotrypsin, and elastase, whereas carboxypeptidase A and B cannot be inhibited [7,46],... 

Poly(acrylic acid)-Bowman-Birk inhibitor conjugate [59], poly(acrylic acid)-chymostatin conjugate [172]... 

Birk, Y. 1985. The Bowman-Birk inhibitor. Int J Pept Protein Res 25 113. 

Chymotrypsin Aprotinin, benzyloxycarbonyl-Pro-Phe-CHO, Bowman-Birk inhibitor, chicken ovoinhibitor, chymostatin, 4-(4-isopropyl piperadinocarbonyl)phenyl 1,2,3,4-tetrahydro-l-naphthoate methanesulphonate, soybean trypsin inhibitor... 

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