bowman birk soybean trypsin inhibitor


Summary: A low-molecular-weight protein (minimum molecular weight 8000) which has the ability to inhibit trypsin as well as chymotrypsin at independent binding sites. It is characterized by a high cystine content and the absence of glycine.

Top Publications

  1. Clemente A, MacKenzie D, Jeenes D, Domoney C. The effect of variation within inhibitory domains on the activity of pea protease inhibitors from the Bowman-Birk class. Protein Expr Purif. 2004;36:106-14 pubmed
    ..Differences in trypsin and chymotrypsin specific inhibitory activities, and in inhibition constants, were observed in studies of the two recombinant variants and BBI. ..
  2. Scarafoni A, Consonni A, Galbusera V, Negri A, Tedeschi G, Rasmussen P, et al. Identification and characterization of a Bowman-Birk inhibitor active towards trypsin but not chymotrypsin in Lupinus albus seeds. Phytochemistry. 2008;69:1820-5 pubmed publisher
    ..The interest in these serine-protease inhibitors arises from the ability to prevent or suppress carcinogen-induced transformation, as shown in various in vitro and in vivo model systems...
  3. Hammond R, Foard D, Larkins B. Molecular cloning and analysis of a gene coding for the Bowman-Birk protease inhibitor in soybean. J Biol Chem. 1984;259:9883-90 pubmed
    ..DNA sequence analysis of the genomic clone reveals that it is similar, although not identical, to the cDNA clone and that it contains no intervening sequences. ..
  4. Kennedy A, Todd P. Biological countermeasures in space radiation health. Gravit Space Biol Bull. 2003;16:37-44 pubmed
    ..Research related to the dietary additions of agents to minimize the risks of developing health-related problems which can result from exposure to space radiations is reviewed. ..
  5. Brauer A, Kelly G, McBride J, Cooke R, Matthews S, Leatherbarrow R. The Bowman-Birk inhibitor reactive site loop sequence represents an independent structural beta-hairpin motif. J Mol Biol. 2001;306:799-807 pubmed
    ..The relationship between the conformation of this beta-hairpin and its biological activity is discussed. ..
  6. Dia V, Berhow M, Gonzalez de Mejia E. Bowman-Birk inhibitor and genistein among soy compounds that synergistically inhibit nitric oxide and prostaglandin E2 pathways in lipopolysaccharide-induced macrophages. J Agric Food Chem. 2008;56:11707-17 pubmed publisher
    ..Furthermore, through their interaction they can modulate the inflammatory process. ..
  7. Dittmann K, Mayer C, Rodemann H. Radioprotection of normal tissue to improve radiotherapy: the effect of the Bowman Birk protease inhibitor. Curr Med Chem Anticancer Agents. 2003;3:360-3 pubmed
    ..Taken together, BBI is recommended as a radioprotector for normal tissue expressing wild type TP53 during treatment of tumors characterized by a mutant TP53. ..
  8. Odani S, Ikenaka T. Studies on soybean trypsin inhibitors. XI. Complete amino acid sequence of a soybean trypsin-chymotrypsin-elastase inhibitor, C-II. J Biochem. 1977;82:1523-31 pubmed
    ..It was found that only a few replacements of one or two amino acid residues around the reactive sites resulted in considerable alteration of the inhibitory specificity. ..
  9. Jaulent A, Leatherbarrow R. Design, synthesis and analysis of novel bicyclic and bifunctional protease inhibitors. Protein Eng Des Sel. 2004;17:681-7 pubmed
    ..It is found that the new inhibitors do indeed allow bifunctional inhibition, although, unlike BBI, the small size of the inhibitor prevents the simultaneous inhibition of two proteases at the same time. ..

More Information


  1. Qi R, Song Z, Chi C. Structural features and molecular evolution of Bowman-Birk protease inhibitors and their potential application. Acta Biochim Biophys Sin (Shanghai). 2005;37:283-92 pubmed
    ..The canonical nine-residue loop of BBIs/STFI-1 provides an ideal template for drug design of specific inhibitors to target their respective proteases. ..
  2. Franssens V, Simonet G, Breugelmans B, Van Soest S, van Hoef V, Vanden Broeck J. The role of hemocytes, serine protease inhibitors and pathogen-associated patterns in prophenoloxidase activation in the desert locust, Schistocerca gregaria. Peptides. 2008;29:235-41 pubmed publisher
    ..On the other hand, real-time PCR analysis revealed that the transcripts, encoding SGPI-1-3, were more abundant in the fat body of immune challenged animals, as compared to control animals. ..
  3. Paine C, Sharlow E, Liebel F, Eisinger M, Shapiro S, Seiberg M. An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway. J Invest Dermatol. 2001;116:587-95 pubmed
    ..These results imply that inhibition of the protease-activated receptor 2 pathway by soymilk may be used as a natural alternative to skin lightening. ..
  4. Malykh E, Larionova N. Study of antiproteinase activity of acylated derivatives of Bowman-Birk soybean proteinase inhibitor. Biochemistry (Mosc). 2002;67:1383-7 pubmed
    ..For mono-, di-, and triacylated BBI derivatives, insertion of two oleic residues into the BBI molecule was demonstrated to be more potent for exhibiting antiproteinase activity. ..
  5. Dittmann K, Mayer C, Kehlbach R, Rodemann H. The radioprotector Bowman-Birk proteinase inhibitor stimulates DNA repair via epidermal growth factor receptor phosphorylation and nuclear transport. Radiother Oncol. 2008;86:375-82 pubmed publisher
    ..TP53 cells only. Since MDC1 is essential for recruitment of DNA repair foci, this observation may explain how BBI selectively stimulated repair of DNA double strand breaks in wt. TP53 cells. ..
  6. Bernkop Schnurch A, Krauland A, Valenta C. Development and in vitro evaluation of a drug delivery system based on chitosan-EDTA BBI conjugate. J Drug Target. 1998;6:207-14 pubmed
    ..It might be a promising formulation for the peroral administration of peptide and protein drugs. ..
  7. Voss R, Ermler U, Essen L, Wenzl G, Kim Y, Flecker P. Crystal structure of the bifunctional soybean Bowman-Birk inhibitor at 0.28-nm resolution. Structural peculiarities in a folded protein conformation. Eur J Biochem. 1996;242:122-31 pubmed
    ..Exposed hydrophobic patches, the presence of charged amino acid residues, and the presence of water molecules in the protein interior are in contrast to standard proteins that comprise a hydrophobic core and exposed polar amino acids. ..
  8. Clementea A, Domoney C. Biological significance of polymorphism in legume protease inhibitors from the Bowman-Birk family. Curr Protein Pept Sci. 2006;7:201-16 pubmed
  9. Gran B, Tabibzadeh N, Martin A, Ventura E, Ware J, Zhang G, et al. The protease inhibitor, Bowman-Birk Inhibitor, suppresses experimental autoimmune encephalomyelitis: a potential oral therapy for multiple sclerosis. Mult Scler. 2006;12:688-97 pubmed
    ..BBIC suppresses EAE, it can be administered orally, and it is safe and relatively inexpensive. It may have a therapeutic role in patients with MS. ..
  10. Baek J, Kim S. Nucleotide sequence of a cDNA encoding soybean Bowman-Birk proteinase inhibitor. Plant Physiol. 1993;102:687 pubmed
  11. Morris C, Morris L, Kennedy A, Sweeney H. Attenuation of skeletal muscle atrophy via protease inhibition. J Appl Physiol (1985). 2005;99:1719-27 pubmed
    ..Thus BBI is a candidate therapeutic agent to minimize skeletal muscle atrophy and loss of strength associated with disuse, cachexia, sepsis, weightlessness, or the combination of age and inactivity. ..
  12. Katano T, Kamata Y, Ueno T, Furuya T, Nakamura T, Ohtsuki K. Biochemical characterization of an effective substrate and potent activators of CK2 copurified with Bowman-Birk-type proteinase inhibitor from soybean seeds in vitro. Biochim Biophys Acta. 2005;1725:47-56 pubmed
  13. Gustin D. Chemoprevention of head and neck cancer. Semin Oncol. 2004;31:769-77 pubmed
    ..Future prospects in the field will also be discussed. ..
  14. Scarpi D, Occhiato E, Trabocchi A, Leatherbarrow R, Brauer A, Nievo M, et al. Introduction of the new dipeptide isostere 7-endo-BtA as reverse turn inducer in a Bowman-Birk proteinase inhibitor: synthesis and conformational analysis. Bioorg Med Chem. 2001;9:1625-32 pubmed
  15. Touil T, Ciric B, Ventura E, Shindler K, Gran B, Rostami A. Bowman-Birk inhibitor suppresses autoimmune inflammation and neuronal loss in a mouse model of multiple sclerosis. J Neurol Sci. 2008;271:191-202 pubmed publisher
    ..BBI reduces inflammation and attenuates neuronal loss, making it an excellent candidate for oral therapy in MS. BBI likely ameliorates EAE by inhibiting multiple pathways involved in disease pathogenesis. ..
  16. Caggana M, Kennedy A. c-fos mRNA levels are reduced in the presence of antipain and Bowman-Birk inhibitor. Carcinogenesis. 1989;10:2145-8 pubmed
    ..As BBI is capable of affecting c-fos gene expression in cells without being present in the nucleus, our results suggest that a novel pathway could be involved in c-fos gene expression. ..
  17. Clemente A, Moreno F, Marín Manzano M, Jiménez E, Domoney C. The cytotoxic effect of Bowman-Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases. Mol Nutr Food Res. 2010;54:396-405 pubmed publisher
    ..The anti-proliferative properties of BBI isoinhibitors from soybean reveal that both trypsin- and chymotrypsin-like proteases involved in carcinogenesis should be considered as potential targets of BBI-like proteins. ..
  18. Mulvenna J, Foley F, Craik D. Discovery, structural determination, and putative processing of the precursor protein that produces the cyclic trypsin inhibitor sunflower trypsin inhibitor 1. J Biol Chem. 2005;280:32245-53 pubmed
    ..The precursor reported here also indicates that despite strong active site sequence homology, SFTI-1 has no other similarities with the Bowman-Birk trypsin inhibitors, presenting interesting evolutionary questions. ..
  19. Malkowicz S, Liu S, Broderick G, Wein A, Kennedy A, Levin R. Effect of the Bowman-Birk inhibitor (a soy protein) on in vitro bladder neck/urethral and penile corporal smooth muscle activity. Neurourol Urodyn. 2003;22:54-7 pubmed
    ..The data suggest that the phytochemical BBI may promote physiologic effects of urethral relaxation and improved voiding by unique mechanisms and deserves further study as a pharmacologic agent for lower urinary tract symptoms. ..
  20. Eckelkamp C, Ehmann B, Schopfer P. Wound-induced systemic accumulation of a transcript coding for a Bowman-Birk trypsin inhibitor-related protein in maize (Zea mays L.) seedlings. FEBS Lett. 1993;323:73-6 pubmed
  21. Meyskens F. Development of Bowman-Birk inhibitor for chemoprevention of oral head and neck cancer. Ann N Y Acad Sci. 2001;952:116-23 pubmed
    ..Additionally, evidence for a dose-related treatment effect of BBIC on oral leukoplakia was demonstrated. These results indicate that BBIC should be investigated for chemopreventive activity in a randomized clinical trial. ..
  22. Nagano H, To K. Purification of collagenase and specificity of its related enzyme from Bacillus subtilis FS-2. Biosci Biotechnol Biochem. 2000;64:181-3 pubmed
    ..The protease from B. subtilis FS-2 culture digested acid casein into fragments with hydrophilic and hydrophobic amino acids as C-terminals, in particular Asn, Gly, Val, and Ile. ..
  23. Fontanini D, Jones B. SEP-1 - a subtilisin-like serine endopeptidase from germinated seeds of Hordeum vulgare L. cv. Morex. Planta. 2002;215:885-93 pubmed
  24. Werle M, Kafedjiiski K, Kolmar H, Bernkop Schnurch A. Evaluation and improvement of the properties of the novel cystine-knot microprotein McoEeTI for oral administration. Int J Pharm. 2007;332:72-9 pubmed
    ..In conclusion, this study indicates that McoEeTI represents a promising candidate as a novel scaffold for oral peptide drug delivery. ..
  25. Gladysheva I, Moroz N, Karmakova T, Nemtsova E, Yakubovskaya R, Larionova N. Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. J Drug Target. 2001;9:303-16 pubmed
    ..These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting. ..
  26. Ragg E, Galbusera V, Scarafoni A, Negri A, Tedeschi G, Consonni A, et al. Inhibitory properties and solution structure of a potent Bowman-Birk protease inhibitor from lentil (Lens culinaris, L) seeds. FEBS J. 2006;273:4024-39 pubmed
    ..The inhibitory properties of LCTI, related to the simultaneous presence of two key amino acids (Gln18 and His54), render the molecule unusual within the natural Bowman-Birk inhibitor family...
  27. Losso J. The biochemical and functional food properties of the bowman-birk inhibitor. Crit Rev Food Sci Nutr. 2008;48:94-118 pubmed publisher
  28. McBride J, Leatherbarrow R. Synthetic peptide mimics of the Bowman-Birk inhibitor protein. Curr Med Chem. 2001;8:909-17 pubmed
  29. Wan X, Meyskens F, Armstrong W, Taylor T, Kennedy A. Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor. Cancer Epidemiol Biomarkers Prev. 1999;8:601-8 pubmed
    ..By inhibiting the cleavage of neu protein on the cell surface, BBI could prevent malignant and premalignant cells expressing high levels of neu protein antigen from escaping host immunological surveillance control. ..
  30. Wan X, Ware J, Zhang L, Newberne P, Evans S, Clark L, et al. Treatment with soybean-derived Bowman Birk inhibitor increases serum prostate-specific antigen concentration while suppressing growth of human prostate cancer xenografts in nude mice. Prostate. 1999;41:243-52 pubmed
    ..Treatment with BBI or BBIC decreased the final tumor load and increased the tumor doubling time and PSA density in the nude mice bearing human prostate cancer xenografts. BBI and/or BBIC could be useful for prostate cancer treatment. ..
  31. Vogtentanz G, Collier K, Bodo M, Chang J, Day A, Estell D, et al. A Bacillus subtilis fusion protein system to produce soybean Bowman-Birk protease inhibitor. Protein Expr Purif. 2007;55:40-52 pubmed
    ..After purification, an average of 72 mg of active sBBI were obtained from 1L of culture broth representing an overall yield of 21% based on the amount of sBBI activated before purification. ..
  32. Ho V, Ng T. A Bowman-Birk trypsin inhibitor with antiproliferative activity from Hokkaido large black soybeans. J Pept Sci. 2008;14:278-82 pubmed
    ..The trypsin inhibitor inhibited HIV-1 reverse transcriptase with an IC50 of 38 microM, but was devoid of antifungal activity toward Fusarium oxysporum and Mycosphaerella arachidicola. ..
  33. Tanaka A, Sampaio M, Mentele R, Auerswald E, Sampaio C. Sequence of a new Bowman-Birk inhibitor from Torresea acreana seeds and comparison with Torresea cearensis trypsin inhibitor (TcTI2). J Protein Chem. 1996;15:553-60 pubmed
    ..The latter was tenfold more effectively inhibited by TcTI2 then by TaTI. Neither TaTI nor TcTI2 affects thrombin, plasma kallikrein, or factor Xa. ..
  34. Park J, Jeong H, Lumen B. In vitro digestibility of the cancer-preventive soy peptides lunasin and BBI. J Agric Food Chem. 2007;55:10703-6 pubmed
    ..The role of other soy protease inhibitors such as Kunitz Trypsin Inhibitor (KTI) cannot be excluded from these experiments. ..
  35. Dittmann K, Gueven N, Mayer C, Rodemann H. Characterization of the amino acids essential for the photo- and radioprotective effects of a Bowman-Birk protease inhibitor-derived nonapeptide. Protein Eng. 2001;14:157-60 pubmed
  36. Malkowicz S, McKenna W, Vaughn D, Wan X, Propert K, Rockwell K, et al. Effects of Bowman-Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia. Prostate. 2001;48:16-28 pubmed
    ..The data obtained in this trial, particularly the data suggesting that BBIC treatment may lead to reduced serum PSA levels and reduced prostate volumes, suggest that a Phase II clinical trial of BBIC for the therapy of BPH is warranted. ..
  37. Seppälä U, Majamaa H, Turjanmaa K, Helin J, Reunala T, Kalkkinen N, et al. Identification of four novel potato (Solanum tuberosum) allergens belonging to the family of soybean trypsin inhibitors. Allergy. 2001;56:619-26 pubmed
  38. Kobayashi H, Suzuki M, Kanayama N, Terao T. A soybean Kunitz trypsin inhibitor suppresses ovarian cancer cell invasion by blocking urokinase upregulation. Clin Exp Metastasis. 2004;21:159-66 pubmed
    ..In conclusion, KTI, but not BBI, could inhibit cell invasiveness at least through suppression of uPA signaling cascade, although the mechanisms of KTI may be different from those of bikunin. ..
  39. Park H, Lin Q, Hamilton A. Modulation of protein-protein interactions by synthetic receptors: design of molecules that disrupt serine protease-proteinaceous inhibitor interaction. Proc Natl Acad Sci U S A. 2002;99:5105-9 pubmed
  40. Marin Manzano M, Ruiz R, Jiménez E, Rubio L, Clemente A. Anti-carcinogenic soyabean Bowman-Birk inhibitors survive faecal fermentation in their active form and do not affect the microbiota composition in vitro. Br J Nutr. 2009;101:967-71 pubmed
    ..BBI retains significance, therefore, as a bioactive compound in the human GIT. ..
  41. Oliva M, Sampaio M. Action of plant proteinase inhibitors on enzymes of physiopathological importance. An Acad Bras Cienc. 2009;81:615-21 pubmed
    ..Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models. ..
  42. Saito T, Sato H, Virgona N, Hagiwara H, Kashiwagi K, Suzuki K, et al. Negative growth control of osteosarcoma cell by Bowman-Birk protease inhibitor from soybean; involvement of connexin 43. Cancer Lett. 2007;253:249-57 pubmed
    ..These results suggest that a major negative growth effect of BBI is based on the restoration of Cx43 expression in U2OS cells. ..
  43. Daly N, Chen Y, Foley F, Bansal P, Bharathi R, Clark R, et al. The absolute structural requirement for a proline in the P3'-position of Bowman-Birk protease inhibitors is surmounted in the minimized SFTI-1 scaffold. J Biol Chem. 2006;281:23668-75 pubmed
    ..Overall, this mutational analysis of SFTI-1 clearly defines the optimized nature of the SFTI-1 scaffold and demonstrates the importance of the secondary loop in maintaining the active conformation of the binding loop. ..
  44. Johnson W, Dooley L, Morrissey R, Arp L, Kapetanovic I, Crowell J, et al. Oncogenicity evaluations of chemopreventive soy components in p53((+/-)) (p53 knockout) mice. Int J Toxicol. 2006;25:219-28 pubmed
    ..By contrast, the positive-control article, p-cresidine, induced urinary bladder cancers in both studies. Neither PTI G-2535 nor BBIC demonstrates any evidence of oncogenicity in the p53((+/-)) mouse model. ..
  45. Chen Y, Huang S, Lin Shiau S, Lin J. Bowman-Birk inhibitor abates proteasome function and suppresses the proliferation of MCF7 breast cancer cells through accumulation of MAP kinase phosphatase-1. Carcinogenesis. 2005;26:1296-306 pubmed
    ..Our results support the notion that proteasome inhibition by BBI is a novel mechanism that contributes to prevention of cancer and further provides evidence that soybean products have the potential to advance as chemopreventive agents. ..
  46. Mello M, Tanaka A, Silva Filho M. Molecular evolution of Bowman-Birk type proteinase inhibitors in flowering plants. Mol Phylogenet Evol. 2003;27:103-12 pubmed
    ..In addition, we found that BBIs from monocotyledonous plants were highly variable, indicating an interesting process of evolution based on internal gene duplications and mutation events. ..
  47. McCormick D, Johnson W, Bosland M, Lubet R, Steele V. Chemoprevention of rat prostate carcinogenesis by soy isoflavones and by Bowman-Birk inhibitor. Nutr Cancer. 2007;57:184-93 pubmed
  48. Clemente A, Gee J, Johnson I, MacKenzie D, Domoney C. Pea (Pisum sativum L.) protease inhibitors from the Bowman-Birk class influence the growth of human colorectal adenocarcinoma HT29 cells in vitro. J Agric Food Chem. 2005;53:8979-86 pubmed
    ..The relative effectiveness of rTI1B and rTI2B may correlate with a variant amino acid sequence within their respective chymotrypsin inhibitory domain, in agreement with a chymotrypsin-like protease as a potential target. ..
  49. Dittmann K, Toulany M, Classen J, Heinrich V, Milas L, Rodemann H. Selective radioprotection of normal tissues by Bowman-birk proteinase inhibitor (BBI) in mice. Strahlenther Onkol. 2005;181:191-6 pubmed
    ..BBI acts as a potent selective normal-tissue radioprotector in vitro and in vivo, apparently without protecting tumors, and thus has the potential to improve clinical radiotherapy. ..
  50. Losso J, Munene C, Bansode R, Bawadi H. Inhibition of matrix metalloproteinase-1 activity by the soybean Bowman-Birk inhibitor. Biotechnol Lett. 2004;26:901-5 pubmed
  51. Singh R, Appu Rao A. Reductive unfolding and oxidative refolding of a Bowman-Birk inhibitor from horsegram seeds (Dolichos biflorus): evidence for "hyperreactive" disulfide bonds and rate-limiting nature of disulfide isomerization in folding. Biochim Biophys Acta. 2002;1597:280-91 pubmed
    ..5 (PPI/inhibitor), there was 1.4-fold enhancement of the folding rate, indicating that the prolyl imidic bond isomerizations may be slowing down the folding reaction but were not rate limiting. ..
  52. Kennedy A. The Bowman-Birk inhibitor from soybeans as an anticarcinogenic agent. Am J Clin Nutr. 1998;68:1406S-1412S pubmed publisher
    ..34671; sponsor, Ann R Kennedy), and studies to evaluate BBIC as an anticarcinogenic agent in human populations began. Both BBI and BBIC prevent and suppress malignant transformation in vitro and carcinogenesis in vivo without toxicity. ..
  53. von Hofe E, Brent R, Kennedy A. Inhibition of X-ray-induced exencephaly by protease inhibitors. Radiat Res. 1990;123:108-11 pubmed
    ..Given our results, further investigation is warranted into preventive effects of protease inhibitors on the inhibition of neural tube defects. ..