Abstract
Proteinase inhibitors are a class of the various dietary inhibitors of mutagenesis and carcinogenesis (Hayatsu et al., 1988). Schelp and Pongpaew (1988) have recently hypothesized that protection against cancer may result from an increase of endogenous proteinase inhibitors such as α2-macroglobulin induced by diets that are low in calories and fat. The Bowman-Birk inhibitor (BBI) of serine proteinases, a double-headed polypeptide-inhibitor of trypsin and chymotrypsin, is one of the most potent cancer chemopreventive agents (Yavelow et al., 1983, 1985). Recently, this property has been substantiated in an in vivo investigation using mice (St. Clair et al., 1990) that were exposed to dimethylhydrazine, a potent chemical carcinogen. Therefore, BBI is currently being considered as an attractive candidate for studies directed toward the prevention of several forms of cancer that are widespread in Western societies. BBI is a small single-chain polypeptide of 71 amino acids with two subdomains directed toward trypsin and chymotrypsin/elastase, respectively (Fig. 1). This protein is the prototype of a family of proteinase inhibitors occurring in legumes. The three-dimensional structure of several BBI-type proteinase inhibitors in the free form (Suzuki et al., 1987; Chen et al., 1992) and complexed with trypsin (Tsunogae et al., 1986) were published recently. The structure of BBI in solution has been determined by NMR spectroscopy (Werner and Wemmer, 1991, 1992). The inhibitory subdomains of BBI are rigidified into a polycyclic, clearly arranged and highly conserved structural framework. BBI-type proteinase inhibitors fulfill many of the criteria of an attractive model for protein engineering studies (Fersht, 1985). Presently, major efforts are devoted to the pathophysiological elucidation and pathobiochemical characterization of the role of limited proteolysis in the course of malignant transformation. However, these efforts will eventually culminate in the rational design of specific chemical agents directed toward those proteolytic enzymes that are involved in malignant transformation.
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Flecker, P. (1993). Analysis of Structure-Activity Relationships of the Bowman-Birk Inhibitor of Serine Proteinases. In: Troll, W., Kennedy, A.R. (eds) Protease Inhibitors as Cancer Chemopreventive Agents. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2882-1_9
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DOI: https://doi.org/10.1007/978-1-4615-2882-1_9
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