Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

Abstract

Bowman-Birk inhibitors (BBIs) are found primarily in seeds of legumes and in cereal grains. These canonical inhibitors share a highly conserved nine-amino acids binding loop motif CTP1SXPPXC (where P1 is the inhibitory active site, while X stands for various amino acids). They are natural controllers of plants’ endogenous proteases, but they are also inhibitors of exogenous proteases present in microbials and insects. They are considered as plants’ protective agents, as their elevated levels are observed during injury, presence of pathogens, or abiotic stress, i.a. Similar properties are observed for peptides isolated from amphibians’ skin containing 11-amino acids disulfide-bridged loop CWTP1SXPPXPC. They are classified as Bowman-Birk like trypsin inhibitors (BBLTIs). These inhibitors are resistant to proteolysis and not toxic, and they are reported to be beneficial in the treatment of various pathological states. In this review, we summarize up-to-date research results regarding BBIs’ and BBLTIs’ inhibitory activity, immunomodulatory and anti-inflammatory activity, antimicrobial and insecticidal strength, as well as chemopreventive properties.

Characterization of a Bowman–Birk type trypsin inhibitor purified from seeds of Solanum surattense

“…Bowman–Birk inhibitors from monocotyledons with molecular weight ~ 16 kDa have a double-headed structure of two separate functional inhibitory domains. The first reactive domain inhibits trypsin-like serine proteases mainly a positively charged residue (Arg or Lys) and the second domain with a large hydrophobic residue (Trp, Leu, Phe or Tyr) inhibits chymotrypsin-like serine proteases and a short hydrophobic residue (Val or Ile) inhibits elastase 32 , 33 . The peptide sequence of SSTI showed six amino acid residues (S-I-P-P-Q-C) which are observed to be conserved among many members of a Bowman–Birk type inhibitors 34 .…”

“…(Mung bean) 36 – 38 and kunitz-type inhibitors from Peltophorum dubium seeds 27 . Generally, the stability of a BBI type trypsin inhibitors towards physical (temperature, pH) and chemical (reducing agents) denaturants is associated with the presence of several disulfide bonds 33 , 39 .

Figure 3 Stability of purified trypsin inhibitor ( A ) Temperature stability of purified SSTI incubation for 30 min at the indicated temperature, ( B ) pH stability of purified SSTI incubation at different pH for 30 min at 37 °C; The residual trypsin inhibitory activity was measured using BApNA as a substrate.

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Bioactivities of Pseudocereal Fractionated Seed Proteins and Derived Peptides Relevant for Maintaining Human Well-Being

“…The Bowman–Birk protease inhibitor (BBI) from soybean is one of the most studied protease inhibitors. Different mechanisms were proposed to explain the BBI anti-proliferative and anti-inflammatory effects: the capacity to inhibit the proteolytic proteasome 20S activity [ 74 ], whose inhibition may result in the induction of apoptosis [ 75 ]; the inhibition of cathepsin G, elastase, and mast cell chymase, proteases involved in inflammatory processes [ 42 ]; and the reduction of the neutrophil infiltration and TNF-α during inflammation [ 76 ] and the increased production of IL-10, an anti-inflammatory cytokine that plays an important role in suppressing autoimmune diseases [ 34 ]. Intriguingly, seed protease inhibitors with antioxidant properties have been observed [ 73 , 77 , 78 ].…”

Physiologically Active Molecules and Functional Properties of Soybeans in Human Health—A Current Perspective

“…Kunitz and Bowman–Birk types of PIs are found in soybeans and inhibit the activity of chymotrypsin, elastase, and serine proteases [ 75 ]. For the past 40 years, the PIs of soybeans have been discussed primarily as antinutritional inhibitory factors; however, more recently, they have also been highlighted for their apparent anticancer properties [ 76 ]. The mechanism underlying the health benefits of PIs is centered on their antioxidant activity, as trypsin inhibitors have been shown to block the generation of free radicals, thereby preventing cells from being transformed by oxidative damage [ 74 ].…”

“…The mechanism underlying the health benefits of PIs is centered on their antioxidant activity, as trypsin inhibitors have been shown to block the generation of free radicals, thereby preventing cells from being transformed by oxidative damage [ 74 ]. For instance, the Bowman–Birk type PI, which has a chymotrypsin inhibitory effect, inhibits the expression of the oncogene MYC , which encodes c-MYC, reduces the production of hydrogen peroxide, an oxygen radical in the body, and prevents the destruction of DNA’s helical structure and DNA oxidation by inhibiting the function of the tumor promotor 12- o -tetradecanoylphorbal-13-acetate [ 76 , 77 ]. According to a recent study, not only the PIs of soybeans, but also retinoids, garlic acid, epigallocatechin gallate, nicotinic acid, and tamoxifen of some plants also function as cancer-preventing agents that inhibit the production of superoxide radicals or H 2 O 2 by tumor promotor factors, despite their structural differences [ 78 ].…”