Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Maria Luiza Vilela Oliva
 -- 2671 2022-05-12 17:17:56 |
2 update references and layout
Amina Yu
 -10 word(s) 2661 2022-05-13 04:43:49 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Vilela Oliva, M.L.; Bonturi, C.; Teixeira, A.B.; , .; Valente, P.; Macêdo Bezerra Filho, C.; Batista, I. Plant Kunitz Inhibitors and Their Interaction with Proteases. Encyclopedia. Available online: https://encyclopedia.pub/entry/22883 (accessed on 26 December 2024).
Vilela Oliva ML, Bonturi C, Teixeira AB,  , Valente P, Macêdo Bezerra Filho C, et al. Plant Kunitz Inhibitors and Their Interaction with Proteases. Encyclopedia. Available at: https://encyclopedia.pub/entry/22883. Accessed December 26, 2024.
Vilela Oliva, Maria Luiza, Camila Bonturi, Ana Beatriz Teixeira,  , Penélope Valente, Clovis Macêdo Bezerra Filho, Isabel Batista. "Plant Kunitz Inhibitors and Their Interaction with Proteases" Encyclopedia, https://encyclopedia.pub/entry/22883 (accessed December 26, 2024).
Vilela Oliva, M.L., Bonturi, C., Teixeira, A.B., , ., Valente, P., Macêdo Bezerra Filho, C., & Batista, I. (2022, May 12). Plant Kunitz Inhibitors and Their Interaction with Proteases. In Encyclopedia. https://encyclopedia.pub/entry/22883
Vilela Oliva, Maria Luiza, et al. "Plant Kunitz Inhibitors and Their Interaction with Proteases." Encyclopedia. Web. 12 May, 2022.
Plant Kunitz Inhibitors and Their Interaction with Proteases
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms23094742

Plant Kunitz inhibitors generally exhibit highly conserved primary structures. These inhibitors usually have a reactive site located in the region that binds to the enzyme, and the formation of the enzyme–inhibitor complex occurs in 1:1 stoichiometry. Their reactive sites are frequently composed of Arg and Lys; they may occasionally contain Glu, Ala, or Val.

cancer insecticide protease inhibitor Kunitz

1. Plant Kunitz Inhibitors

Although widely distributed in nature, plant Kunitz inhibitors (I3) are especially abundant in the Fabaceae (Leguminosae) family, which comprises the Mimosoideae, Caesalpinioideae, and Faboideae/Papilionoideae subfamilies [1]. The Soybean Kunitz trypsin inhibitor (SKTI) was the first member of this family to be identified [2], and was reported by M. Kunitz; inhibitors subsequently discovered that share similar characteristics are therefore named Kunitz inhibitors. Generally, Kunitz inhibitors are defense proteins, which exhibit different activities as highlighted, including antibacterial and antifungal activities, and act on inflammation, coagulation, thrombosis, and cancer.
Plant Kunitz inhibitors generally exhibit highly conserved primary structures. These inhibitors usually have a reactive site located in the region that binds to the enzyme, and the formation of the enzyme–inhibitor complex occurs in 1:1 stoichiometry. Their reactive sites are frequently composed of Arg and Lys; however, they may occasionally contain Glu, Ala, or Val [3]. These inhibitors can be single- or double-polypeptide-chain proteins, with variation in the number of cysteine residues and disulfide bridge patterns. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) [4] and Bauhinia rufa trypsin inhibitor (BrTI) [5] are single-chain inhibitors lacking cysteine residues. The B. bauhinioides kallikrein inhibitor (BbKI) is also a single-chain inhibitor; however, it contains one cysteine residue [6][7]. The B. rufa elastase inhibitor (gBrEI) [8], Swartzia pickellii trypsin inhibitor (SWTI) [9], Entada scandens trypsin inhibitor (ESTI) [10], and Inga laurina trypsin inhibitor (IlTI) [11] are single-chain inhibitors with two cysteine residues. Although the Copaifera langsdorffii inhibitor (ClI) also contains two cysteines, it is a double-chain inhibitor, with the chains linked through noncovalent bridges [12]. The classic Kunitz-type inhibitors, soybean trypsin inhibitor (STI) [13], and Bauhinia variegata var. candida trypsin inhibitor (BvTI-C) [14] are single-polypeptide-chain proteins that possess four cysteines. The Enterolobium contortisiliquum trypsin inhibitor (EcTI) [15][16] and Acacia karroo trypsin inhibitor (AkTI) [17] also contain four cysteines; however, they are double-polypeptide-chain proteins linked by two S–S bridges. Canavalia lineata subtilisin inhibitor type II (CLSI-II) is a similar double-chain inhibitor linked by two S–S bridges, but contains five Cys residues, four of which are linked with bridges and one is a free cysteine [18]. These profiles are summarized in Figure 1.
Ijms 23 04742 g001 550
Figure 1. Structural aspects of plant Kunitz inhibitors in terms of the number of cysteine residues (0, 1, 2, 4, or 5 Cys), S–S bridges (none, intrachain and/or interchain bridges), and polypeptide chain representation (single or double chains).

The same research group obtained rBbKIm based on the primary sequence of BbKI, but incorporated the RGD/RGE (Arg–Gly–Asp/Arg–Gly–Glu) motifs from BrTI. To this end, the mutations V21E, S24A, H25R, H27D, A28G, E127D, and Q130E were introduced into BbKI. The importance of these residues in the defense against predatory insects has been demonstrated [19]. This inhibitor also interfered with the viability of prostate cancer DU145 and PC3 cells, leading to cell death via the release of cytochrome c and caspase-3 activation [20].

Moreover, the Ligusticum chuanxiong subtilisin/alpha-amylase inhibitor (LASI), expressed in E. coli Rosetta and obtained from the rhizome of L. chuanxiong (frequently used in Chinese medicine to treat headaches, cardiovascular diseases, rheumatic joint pain, menstrual disorders, and painful swelling), was also obtained as a recombinant protein. LASI inhibits mammalian alpha-amylase and bacterial subtilisin (which may be involved in the protection of plants against microorganisms) and also affects pest lepidopterans, which are all relevant for agricultural applications. Although LASI shares sequence similarities with other Kunitz protease inhibitors, such as Cynara cardunculus (68%), it has a unique reactive site; consequently, LASI inhibits subtilisin but does not affect trypsin or chymotrypsin. Furthermore, LASI inhibits alpha-amylase from Plutella xylostella, Helicoverpa armigera, and Spodoptera litura, thereby reducing the survival of these pests [21].
The insecticidal properties of the Cassia obtusifolia trypsin inhibitor (CoTI1) have also been described [22]. CoTI1 was used to investigate stress tolerance and increase the resistance of crops against pests. It is a potent trypsin inhibitor (2.490 UI/mg activity) and also inhibits trypsin-like proteases from H. armigera, S. litura, and S. exigua (1.770 UI/mg, 1.510 UI/mg, and 1.210 UI/mg, respectively). The amino acids L84, R86, and T88 in CoTI1 were identified, using in silico analysis, as being involved in trypsin inhibition, which was further confirmed by the loss of inhibitory activity (54%, 90%, and 53%, respectively) on mutating these residues to alanine.
Inhibition of human neutrophil elastase (HNE) is known to be beneficial in modulating inflammatory lung diseases. The Caesalpinia echinata elastase inhibitor (CeEI), which inhibits HNE, has been used to study pulmonary inflammation [23]. Native CeEI is a potent inhibitor of HNE (Ki 1.9 nM), cathepsin G (CatG, Ki 3.6 nM), and protease 3 (Ki 3.7 μM). Two recombinant isoinhibitors of CeEI, rCeEI-4, and rCeEI-5 were cloned and expressed in E. coli. rCeEI-5 inhibited HNE 6.2 times more efficiently than CeEI, while rCeEI-4 exhibited 4.2-fold higher inhibition of chymotrypsin and 5.3-fold higher inhibition of HNE than CeCI. Synthetic, smaller functional peptides that inhibit HNE rCeEI-36 (Ki = 0.3 nM) and rCeEI-46 (Ki = 8.8 nM) were also obtained from the CeEI-4 sequence.
Apios americana, a legume tuber plant widely distributed across North America, is commonly used to make bread in Japan [24]. This plant produces two Kunitz-type protease inhibitors, Apios americana protease inhibitor 1 (AKPI-1) and Apios americana protease inhibitor 2 (AKPI-2), which were cloned and expressed as recombinant proteins. rAKPI-2, characterized as chymotrypsin (Ki 6 µM) and trypsin inhibitor (Ki 0.4 µM), loses its property of trypsin inhibition when heated at 70 °C; however, the chymotrypsin inhibitory activity is maintained at 80% of its initial value at the same temperature.
Although most recombinant inhibitors are produced in bacterial hosts, it is also possible to do so with yeast, as achieved by Bunyatang et al. [25]. The PKPI protease inhibitor, a bifunctional inhibitor that acts on protease and amylase, was cloned and transferred into Pichia pastoris to produce a full-length protease inhibitor based on the Hevea brasiliensis inhibitor (HbASI), which showed high activity against alpha-amylase (from Aspergillus oryzae, IC50 200 µg), subtilisin A (IC50 380 µg), and trypsin (IC50 325 µg), but no activity against chymotrypsin and human alpha-amylase. In addition, HbASI showed good stability over a wide temperature and pH range, and inhibited mycelial growth of Phytophthora palmivora (0.2 µM), including 50% inhibition of zoospore .

2. Defense Proteins

Plants can detect events locally and transmit defense signals to build up systemic acquired resistance (SAR). A Kunitz protease inhibitor in the tea plant Camellia sinensis (CsKPI1) was shown to be potentially involved in SAR based on its gene expression, which was strongly induced by insects through localized feeding, and in neighboring undamaged leaves. Jasmonic acid and CsKPI1 were detected simultaneously in damaged leaves; in addition, the jasmonic acid content also increased in neighboring leaves, suggesting its role as a vital hormonal signal that induces the expression of CsKPI1 in SAR [26].
Based on their ability to function as defense proteins that protect against predator attacks, protease inhibitors have been used as insecticidal agents that act by inhibiting digestive proteases in insects, thereby controlling the availability of amino acids for the growth and development of larvae (Figure 2). The Kunitz-type Cassia leiandra trypsin inhibitor (ClTI) inhibits midgut digestive proteases (50% activity reduction at 4.65 µM) and larvae development (after 10 days at a final concentration of 15.4 µM), and delays adult emergence, in Aedes aegypti, causing 44% mortality. These findings suggest that ClTI has the potential to reduce the A. aegypti population without increasing the risk of developing insect resistance [27]. Similarly, alocasin, purified from the rhizome of Alocasia macrorrhiza, increased the mortality rate of A. aegypti larvae and adult females (IC50 = 0.17 mg/mL) by its action against the midgut enzymes of this insect. However, higher inhibitor concentrations lead to a reduction in the inhibitory effect, which may be attributed to the production of insect proteases insensitive to the inhibitor upon prolonged exposure [28]. In another, proteolytic activity was restored on the 15th day after hatching of Anticarsia gemmatalis larvae exposed to SKTI, after a decrease in the total proteolytic activity of trypsin and similar enzymes until the 12th day [29]. On the other hand, the Adenanthera pavonina Kunitz-type inhibitor (ApKTI) acts through a noncompetitive mechanism, thereby offering an advantage over such adaptation mechanisms as its affinity for trypsin is not affected by amino acid mutations in the enzyme active site, unlike other competitive protease inhibitors. Thus, ApKTI showed insecticidal activity even after 15 days of chronic exposure when included in the artificial diet of Plodia interpunctella larvae [30], and achieved a 60% reduction in the survival of neonatal Anticarsia gemmatalis larvae [31]. According to Sasaki et al. [32], A. aegypti larvae also do not use regulatory mechanisms to overcome the effects of ApKTI, and the inhibitor demonstrated degeneration of the microvilli of epithelial cells of the posterior midgut region, hypertrophy of the gastric cecal cells, and an augmented ectoperitrophic space in larvae. Interestingly, although trypsin and chymotrypsin-like serine proteases are involved in the initial protein digestion of Lepidoptera, ILTI (from Inga laurina) inhibits trypsin in the midgut of S. frugiperda more effectively compared to other protease inhibitors, such as SKTI and Inga vera trypsin inhibitor (IVTI). Neither SKTI nor ILTI was active against chymotrypsin. Notably, ILTI was not degraded by enzymes in the midgut of insects, and was stable after elimination in feces, showing resistance to microbial metabolism [33]. IVTI exerted midgut inhibition in S. frugiperda, C. cephalonica, H. virescens, and H. zea of 83%, 80%, 70%, and 64%, respectively [34]. More recently, other inhibitors have been characterized, such as RsKI from Rhynchosia sublobata, which is active against lepidopteran gut proteases, including those of Achaea janata (IC50 = 1.95 µg) and Helicoverpa armigera (IC50 = 59 µg) [35], and the inhibitor CpPI 63, isolated from Cajanus platycarpus seeds, a wild relative of pigeonpea [36].
Ijms 23 04742 g002 550
Figure 2. Uses of protease inhibitors as insecticides, and antibacterial and antifungal agents. The inhibitors are also active in mammal pathologies associated with inflammation, thrombosis, and tumorigenesis.
While protease inhibitors are important in defending against predators, they can also selectively assist in mutualistic relationships. For example, the ant Pseudomyrmex ferrugineus uses Acacia sp. hollow thorns as a nesting space, and while the Acacia sp. provides food bodies and extrafloral nectar for ant larvae, the ant offers protection against herbivores that compete for vegetation. Thus, protease inhibitors extracted from Acacia sp. food bodies are activated and convert the nutritive food reward into something difficult to digest for potential or optional exploiters, but not for mutualistic consumers, whose biochemistry takes advantage of this reward [37].
Cowpeas are an important food source for millions of people worldwide. Many have been used Callosobruchus maculatus [38] and Zabrotes subfasciatus [39] as models to evaluate the effect of protease inhibitors because these beetles cause serious damage to the grain, making it unfit for human consumption. The Pithecellobium dumosum Kunitz inhibitor (PdKI), purified from the seeds of the P. dumosum tree, was evaluated against cysteine and serine proteases extracted from the larvae of coleopterans C. maculatus and Z. subfasciatus and the lepidopterans Alabama argillacea and Telchin licus. It completely inhibited bovine trypsin at 100 nM, with 50% inhibition against bovine chymotrypsin. PdKI showed specificity for serine proteases, especially against those from phytophagous insects, such as Coleoptera and Lepidoptera [40].
Many factors are involved in the adaptability of insects to protease inhibitors, such as the alternative use of other classes of proteases, overexpression of proteases to minimize the inhibitory effect, or the degradation of the inhibitors by nontarget proteases, which are insensitive to the inhibitors. Thus, despite the potential applicability of protease inhibitors as effective compounds for the protection of crops against herbivory, most recent one has been pointed to the importance of multitrophic approaches, taking into account not only target insect proteases, but also proteases from other organisms in the food chain, including the plant itself [41].
Termites are one of the main wood-destroying pests that can invade and attack the wooden building structures in urban environments. While synthetic pesticides are traditionally used to prevent termite attacks, these compounds tend to harm humans and the environment. As an alternative, the trypsin inhibitor isolated from Cassia grandis seeds (CgTI) can be employed, which exhibits termiticidal activity against Nasutitermes corniger. However, the activity has been found to vary between termite castes, with workers (IC50 = 0.685 mg/mL) being more resistant than soldiers (IC50 = 0.765 mg/mL) [42], which can be attributed to variation in enzymatic activities and digestive tracts between the castes. Similar to these results, EcTI was able to induce the death of worker termites, with an IC50 of 0.242 mg/mL, whereas it did not exert significant inhibition in soldier termites. Notably, the molecule from the intestinal extract that binds to EcTI is a chitinase from T. reesei, a symbiotic fungus present in the digestive tract of termites that is important in the cellulose degradation process. As this cellulose is exploited for the production of bioethanol, EcTI could be applied as a biotechnological tool in addition to being a natural active termiticide [43].
In the same line of investigation, two distinct recombinant protease inhibitors of B. bauhinioides origin, rBbKI (serine protease inhibitor) and rBbCI (cysteine protease inhibitor) were evaluated for their termiticidal activity. Despite sharing 82% structural similarity, the two inhibitors showed differing specificity for termite intestinal enzymes, and could be interesting tools for the characterization of N. corniger enzymes. rBbKI showed termiticidal activity in workers, with an LC50 of 0.9 mg/mL after four days, and did not affect the survival of soldiers, whereas rBbCI did not show any termiticidal activity on N. corniger [44]. In another, Araucaria angustifolia pine nut extract was shown to exhibit termiticidal activity against N. corniger workers and soldiers at all tested concentrations [45].
Finally, the bifunctional lectin and Kunitz inhibitor AEL, isolated from Abelmoschus esculentus, was shown to exhibit activity against the fruit fly Ceratitis capitata and the nematodes Meloidogyne incognita and Meloidogyne javanica, which infest plant roots. In the pupal stage of M. incognita, 2 mg/mL AEL showed higher toxicity than organophosphates commonly used in agriculture, exemplifying the potential of protease inhibitors as promising insecticidal molecules [46].

3. Antibacterial and Antifungal Activities

Fungi and bacteria release proteases into the media during infections, which facilitates their defense and survival. Inhibitors of these proteases can therefore hinder pathogen metabolism to improve human health [47]. Plant inhibitors from the Kunitz family may be important in controlling fungal and bacterial growth, as demonstrated by the inhibition of proteases secreted by Bacillus sp. (Figure 2) and Aspergillus flavus induced by extracts from seeds of Cassia tora (L.) syn Senna tora (L.) Roxb [48]. In addition, the isolated protein fraction from Erythrina poeppigiana interferes with the germination of A. flavus spores [49]. ClTI from C. leiandra seeds inhibited the growth of Candida albicans, Candida tropicalis, Candida parapsilosis, and Candida krusei, with values of 5.13 μM, being most potent for C. albicans, with an IC50 of 2.10 μM [50].
Some inhibitors show more restricted specificity, such as the Inga edulis trypsin inhibitor (IeTI). Although it has no action against C. albicans, it is a potent inhibitor of C. tropicalis, as well as Candida buinensis (87% inhibition with 400 μg/mL IeTI). The antifungal activity was found to be mediated by the alteration of the plasma membrane, which diverts energy metabolism from physiological functions to repair it, thereby inducing morphological changes that can affect cell viability or even trigger apoptosis through complexation with vital enzymes in this pathway (Figure 2) [51]. The same mechanism was described with Enterolobium timbouva trypsin inhibitor (EtTI), suggesting that this inhibitor affects the integrity of the plasma membrane of yeasts, inducing the generation of intracellular ROS due to mitochondrial activation to maintain membrane potential, and consequently affecting the organelle structure. In addition, ROS generation is the main cause of DNA damage in yeast, and the mode of action of EtTI appears to involve the activation of apoptosis via a different pathway than traditional antifungal drugs [52][53]. This mechanism is also similar to that used by Pseudostellaria heterophylla trypsin inhibitor (PhTI), a 20.5 kDa thermostable inhibitor that has been reported to show potent activity against the pathogenic fungi Candida gloeosporioides and Fusarium oxysporum. The inhibitor also exhibits high stability, suggesting its potential for use as an antifungal protein in the food industry and agriculture [54].

References

  1. Oliva, M.L.V.; Silva, M.C.; Sallai, R.C.; Brito, M.V.; Sampaio, M.U. A novel subclassification for Kunitz proteinase inhibitors from leguminous seeds. Biochimie 2010, 92, 1667–1673.
  2. Kunitz, M. Crystallization of a Trypsin Inhibitor from Soybean. Science 1945, 101, 668–669.
  3. Bendre, A.D.; Ramasamy, S.; Suresh, C.G. Analysis of Kunitz inhibitors from plants for comprehensive structural and functional insights. Int. J. Biol. Macromol. 2018, 113, 933–943.
  4. Hansen, D.; Macedo-Ribeiro, S.; Veríssimo, P.; Im, S.Y.; Sampaio, M.U.; Oliva, M.L.V. Crystal structure of a novel cysteinless plant Kunitz-type protease inhibitor. Biochem. Biophys. Res. Commun. 2007, 360, 735–740.
  5. Nakahata, A.M.; Bueno, N.R.; Rocha, H.A.; Franco, C.R.; Chammas, R.; Nakaie, C.R.; Jasiulionis, M.; Nader, H.B.; Santana, L.A.; Sampaio, M.U.; et al. Structural and inhibitory properties of a plant proteinase inhibitor containing the RGD motif. Int. J. Biol. Macromol. 2006, 40, 22–29.
  6. Zhou, D.; Hansen, D.; Shabalin, I.G.; Gustchina, A.; Vieira, D.F.; De Brito, M.V.; Araujo, A.P.U.; Oliva, M.L.; Wlodawer, A. Structure of BbKI, a disulfide-free plasma kallikrein inhibitor. Acta Crystallogr. Sect. F Struct. Biol. Commun. 2015, 71 Pt 8, 1055–1062.
  7. Li, M.; Srp, J.; Gustchina, A.; Dauter, Z.; Mares, M.; Wlodawer, A. Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes. Acta Crystallogr. Sect. D Struct. Biol. 2019, 75, 56–69.
  8. Sumikawa, J.T.; Nakahata, A.M.; Fritz, H.; Mentele, R.; Sampaio, M.U.; Oliva, M.L. A Kunitz-Type Glycosylated Elastase Inhibitor with One Disulfide Bridge. Planta Med. 2006, 72, 393–397.
  9. Cavalcanti, M.D.S.M.; Oliva, M.L.; Fritzc, H.; Jochumc, M.; Mentelec, R.; Sampaiob, M.; Coelho, L.C.; Batista, I.F.; Sampaio, C.A. Characterization of a Kunitz Trypsin Inhibitor with One Disulfide Bridge Purified from Swartzia pickellii. Biochem. Biophys. Res. Commun. 2002, 291, 635–639.
  10. Lingaraju, M.H.; Gowda, L.R. A Kunitz trypsin inhibitor of Entada scandens seeds: Another member with single disulfide bridge. Biochim. Biophys. Acta (BBA) Proteins Proteom. 2008, 1784, 850–855.
  11. Macedo, M.L.; Garcia, V.A.; Freire, M.D.; Richardson, M. Characterization of a Kunitz trypsin inhibitor with a single disulfide bridge from seeds of Inga laurina (SW.) Willd. Phytochemistry 2007, 68, 1104–1111.
  12. Krauchenco, S.; Nagem, R.A.; da Silva, J.A.; Marangoni, S.; Polikarpov, I. Three-dimensional structure of an unusual Kunitz (STI) type trypsin inhibitor from Copaifera langsdorffii. Biochimie 2004, 86, 167–172.
  13. Song, H.K.; Suh, S.W. Kunitz-type soybean trypsin inhibitor revisited: Refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator. J. Mol. Biol. 1998, 275, 347–363.
  14. Di Ciero, L.; Oliva, M.L.; Torquato, R.; Köhler, P.; Weder, J.K.; Novello, C.J.; Sampaio, C.A.; Oliveira, B.; Marangoni, S. The complete amino acid sequence of a trypsin inhibitor from Bauhinia variegata var. candida seeds. J. Protein Chem. 1998, 17, 827–834.
  15. Batista, I.F.; Nonato, M.C.; Bonfadini, M.R.; Beltramini, L.M.; Oliva, M.L.; Sampaio, M.U.; Sampaio, C.A.; Garratt, R.C. Preliminary crystallographic studies of EcTI, a serine proteinase inhibitor from Enterolobium contortisiliquum seeds. Acta Crystallogr. Sect. D Biol. Crystallogr. 2001, 57, 602–604.
  16. Zhou, D.; Lobo, Y.; Batista, I.F.; Marques-Porto, R.; Gustchina, A.; Oliva, M.L.; Wlodawer, A. Crystal Structures of a Plant Trypsin Inhibitor from Enterolobium contortisiliquum (EcTI) and of Its Complex with Bovine Trypsin. PLoS ONE 2013, 8, e62252.
  17. Patthy, A.; Molnár, T.; Porrogi, P.; Naude, R.; Gráf, L. Isolation and characterization of a protease inhibitor from Acacia karroo with a common combining loop and overlapping binding sites for chymotrypsin and trypsin. Arch. Biochem. Biophys. 2015, 565, 9–16.
  18. Terada, S.; Katayama, H.; Noda, K.; Fujimura, S.; Kimoto, E. Amino Acid Sequences of Kunitz Family Subtilisin Inhibitors from Seeds of Canavalia lineata. J. Biochem. 1994, 115, 397–404.
  19. Sumikawa, J.T.; Brito, M.V.; Araújo, A.P.U.; Macedo, M.L.; Oliva, M.L.V.; Miranda, A. Action of Bauhinia-derivated compounds on Callosobruchus maculatus development. Adv. Exp. Med. Biol. 2009, 611, 563–564.
  20. Ferreira, J.G.; Diniz, P.M.M.; de Paula, C.A.A.; Lobo, Y.A.; Gamero, E.J.P.; Paschoalin, T.; Nogueira-Pedro, A.; Maza, P.K.; Toledo, M.S.; Suzuki, E.; et al. The Impaired Viability of Prostate Cancer Cell Lines by the Recombinant Plant Kallikrein Inhibitor. J. Biol. Chem. 2013, 288, 13641–13654.
  21. Yu, J.-H.; Li, Y.-Y.; Xiang, M.; Zhu, J.-Q.; Huang, X.-H.; Wang, W.-J.; Tan, R.; Zhou, J.-Y.; Liao, H. Molecular cloning and characterization of α-amylase/subtilisin inhibitor from rhizome of Ligusticum chuanxiong. Biotechnol. Lett. 2016, 39, 141–148.
  22. Liu, Z.; Zhu, Q.; Li, J.; Zhang, G.; Jiamahate, A.; Zhou, J.; Liao, H. Isolation, structure modeling and function characterization of a trypsin inhibitor from Cassia obtusifolia. Biotechnol. Lett. 2015, 37, 863–869.
  23. Cruz-Silva, I.; Gozzo, A.J.; Nunes, V.A.; Tanaka, A.S.; Araujo, M.D.S. Bioengineering of an elastase inhibitor from Caesalpinia echinata (Brazil wood) seeds. Phytochemistry 2021, 182, 112595.
  24. Liu, J.; Yonekura, M.; Kouzuma, Y. Purification, cDNA cloning and characterization of Kunitz-type protease inhibitors from Apios americana tubers. Biosci. Biotechnol. Biochem. 2020, 84, 563–574.
  25. Bunyatang, O.; Chirapongsatonkul, N.; Bangrak, P.; Henry, R.; Churngchow, N. Molecular cloning and characterization of a novel bi-functional α-amylase/subtilisin inhibitor from Hevea brasiliensis. Plant Physiol. Biochem. 2016, 101, 76–87.
  26. Zhu, J.; He, Y.; Yan, X.; Liu, L.; Guo, R.; Xia, X.; Cheng, D.; Mi, X.; Samarina, L.; Liu, S.; et al. Duplication and transcriptional divergence of three Kunitz protease inhibitor genes that modulate insect and pathogen defenses in tea plant (Camellia sinensis). Hortic. Res. 2019, 6, 126.
  27. Dias, L.P.; Oliveira, J.T.; Rocha-Bezerra, L.C.; Sousa, D.O.; da Costa, H.P.S.; Araujo, N.M.; Carvalho, A.F.; Tabosa, P.M.; Monteiro-Moreira, A.C.; Lobo, M.D.; et al. A trypsin inhibitor purified from Cassia leiandra seeds has insecticidal activity against Aedes aegypti. Process Biochem. 2017, 57, 228–238.
  28. Vajravijayan, S.; Pletnev, S.; Pletnev, V.Z.; Nandhagopal, N.; Gunasekaran, K. Crystal structure of a novel Kunitz type inhibitor, alocasin with anti-Aedes aegypti activity targeting midgut proteases. Pest Manag. Sci. 2018, 74, 2761–2772.
  29. Mendonça, E.G.; Barros, R.A.; Cordeiro, G.; Silva, C.R.; Campos, W.G.; Oliveira, J.A.; Oliveira, M.G.A. Larval development and proteolytic activity of Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae) exposed to different soybean protease inhibitors. Arch. Insect Biochem. Physiol. 2020, 103, e21637.
  30. De Oliveira, C.; Flores, T.M.D.O.; Cardoso, M.H.; Oshiro, K.G.N.; Russi, R.; de França, A.; Dos Santos, E.A.; Franco, O.L.; De Oliveira, A.S.; Migliolo, L. Dual Insecticidal Effects of Adenanthera pavonina Kunitz-Type Inhibitor on Plodia interpunctella is Mediated by Digestive Enzymes Inhibition and Chitin-Binding Properties. Molecules 2019, 24, 4344.
  31. Meriño-Cabrera, Y.; Mendes, T.A.D.O.; Castro, J.; Barbosa, S.L.; Macedo, M.; Oliveira, M.G.A. Noncompetitive tight-binding inhibition of Anticarsia gemmatalis trypsins by Adenanthera pavonina protease inhibitor affects larvae survival. Arch. Insect Biochem. Physiol. 2020, 104, e21687.
  32. Sasaki, D.Y.; Jacobowski, A.C.; de Souza, A.P.; Cardoso, M.H.; Franco, O.L.; Macedo, M.L.R. Effects of proteinase inhibitor from Adenanthera pavonina seeds on short- and long term larval development of Aedes aegypti. Biochimie 2015, 112, 172–186.
  33. Machado, S.W.; De Oliveira, C.; Zério, N.G.; Parra, J.; Macedo, M. Inga laurina trypsin inhibitor (ILTI) obstructs Spodoptera frugiperda trypsins expressed during adaptive mechanisms against plant protease inhibitors. Arch. Insect Biochem. Physiol. 2017, 95, e21393.
  34. Bezerra, C.S.; de Oliveira, C.F.R.; Machado, O.L.T.; de Mello, G.S.V.; Pitta, M.G.R.; Rêgo, M.J.B.M.; Napoleão, T.H.; Paiva, P.M.G.; Ribeiro, S.D.F.F.; Gomes, V.M.; et al. Exploiting the biological roles of the trypsin inhibitor from Inga vera seeds: A multifunctional Kunitz inhibitor. Process Biochem. 2016, 51, 792–803.
  35. Mohanraj, S.S.; Gujjarlapudi, M.; Lokya, V.; Mallikarjuna, N.; Dutta-Gupta, A.; Padmasree, K. Purification and characterization of Bowman-Birk and Kunitz isoinhibitors from the seeds of Rhynchosia sublobata (Schumach.) Meikle, a wild relative of pigeonpea. Phytochemistry 2019, 159, 159–171.
  36. Swathi, M.; Mishra, P.K.; Lokya, V.; Swaroop, V.; Mallikarjuna, N.; Dutta-Gupta, A.; Padmasree, K. Purification and Partial Characterization of Trypsin-Specific Proteinase Inhibitors from Pigeonpea Wild Relative Cajanus platycarpus L. (Fabaceae) Active against Gut Proteases of Lepidopteran Pest Helicoverpa armigera. Front. Physiol. 2016, 7, 388.
  37. Orona-Tamayo, D.; Wielsch, N.; Blanco-Labra, A.; Svatos, A.; Farías-Rodríguez, R.; Heil, M. Exclusive rewards in mutualisms: Ant proteases and plant protease inhibitors create a lock-key system to protect Acacia food bodies from exploitation. Mol. Ecol. 2013, 22, 4087–4100.
  38. Sanon, A.; Zakaria, I.; Clémentine, L.D.B.; Niango, B.M.; Honora, N.R.C. Potential of Botanicals to Control Callosobruchus maculatus (Col.: Chrysomelidae, Bruchinae), a Major Pest of Stored Cowpeas in Burkina Faso: A Review. Int. J. Insect. Sci. 2018, 10, 1–8.
  39. Mallqui, K.S.V.; Oliveira, E.E.; Guedes, R.N.C. Competition between the bean weevils Acanthoscelides obtectus and Zabrotes subfasciatus in common beans. J. Stored Prod. Res. 2013, 55, 32–35.
  40. Rufino, F.P.; Pedroso, V.M.; Araujo, J.N.; de França, A.F.; Rabelo, L.M.; Migliolo, L.; Kiyota, S.; Santos, E.A.; Franco, O.L.; Oliveira, A.S. Inhibitory effects of a Kunitz-type inhibitor from Pithecellobium dumosum (Benth) seeds against insect-pests’ digestive proteinases. Plant Physiol. Biochem. 2013, 63, 70–76.
  41. Rumpold, B.; Schlüter, O. Insect-based protein sources and their potential for human consumption: Nutritional composition and processing. Anim. Front. 2015, 5, 20–24.
  42. Brandão-Costa, R.; Araújo, V.F.; Porto, A. CgTI, a novel thermostable Kunitz trypsin-inhibitor purified from Cassia grandis seeds: Purification, characterization and termiticidal activity. Int. J. Biol. Macromol. 2018, 118 Pt B, 2296–2306.
  43. Ferreira, R.; Napoleão, T.H.; Silva-Lucca, R.A.; Silva, M.; Paiva, P.M.G.; Oliva, M.L.V. The effects of Enterolobium contortisiliquum serine protease inhibitor on the survival of the termite Nasutitermes corniger, and its use as affinity adsorbent to purify termite proteases. Pest Manag. Sci. 2019, 75, 632–638.
  44. Ferreira, R.S.; Brito, M.V.; Napoleão, T.H.; Silva, M.; Paiva, P.; Oliva, M. Effects of two protease inhibitors from Bauhinia bauhinoides with different specificity towards gut enzymes of Nasutitermes corniger and its survival. Chemosphere 2019, 222, 364–370.
  45. Sallai, R.C.; Salu, B.R.; Silva-Lucca, R.A.; Alves, F.L.; Napoleão, T.H.; Paiva, P.M.G.; Ferreira, R.D.S.; Sampaio, M.U.; Oliva, M.L.V. Biotechnological Potential of Araucaria angustifolia Pine Nuts Extract and the Cysteine Protease Inhibitor AaCI-2S. Plants 2020, 9, 1676.
  46. De Lacerda, J.T.J.G.; Lacerda, R.R.E.; Assunção, N.A.; Tashima, A.K.; Juliano, M.A.; dos Santos, G.A. New insights into lectin from Abelmoschus esculentus seeds as a Kunitz-type inhibitor and its toxic effects on Ceratitis capitata and root-knot nematodes Meloidogyne spp. Process Biochem. 2017, 63, 96–104.
  47. Müller, V.; Bonacci, G.; Batthyány, C.; Amé, M.V.; Carrari, F.; Gieco, J.; Asis, R. Peanut Seed Cultivars with Contrasting Resistance to Aspergillus parasiticus Colonization Display Differential Temporal Response of Protease Inhibitors. Phytopathology 2017, 107, 474–482.
  48. Tripathi, V.R.; Kumar, S.; Garg, S.K. A study on trypsin, Aspergillus flavus and Bacillus sp. protease inhibitory activity in Cassia tora (L.) syn Senna tora (L.) Roxb. seed extract. BMC Complement. Altern. Med. 2011, 11, 56.
  49. Barros, K.M.A.; Sardi, J.D.C.O.; Maria-Neto, S.; Macedo, A.J.; Ramalho, S.R.; de Oliveira, D.G.L.; Macedo, M.L.R. A new Kunitz trypsin inhibitor from Erythrina poeppigiana exhibits antimicrobial and antibiofilm properties against bacteria. Biomed. Pharmacother. 2021, 144, 112198.
  50. Araújo, N.M.; Dias, L.P.; Costa, H.P.; Sousa, D.O.; Vasconcelos, I.M.; de Morais, G.A.; Oliveira, J.T. ClTI, a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds, exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis. Biochim. Biophys. Acta (BBA)-Biomembr. 2019, 1861, 183032.
  51. Dib, H.X.; De Oliveira, D.G.L.; De Oliveira, C.F.R.; Taveira, G.B.; Mello, E.D.O.; Verbisck, N.V.; Chang, M.; Corrêa, D., Jr.; Gomes, V.M.; Macedo, M.L.R. Biochemical characterization of a Kunitz inhibitor from Inga edulis seeds with antifungal activity against Candida spp. Arch. Microbiol. 2018, 201, 223–233.
  52. De Oliveira, C.F.; Oliveira, C.T.; Taveira, G.B.; Mello, E.D.O.; Gomes, V.M.; Macedo, M.L.R. Characterization of a Kunitz trypsin inhibitor from Enterolobium timbouva with activity against Candida species. Int. J. Biol. Macromol. 2018, 119, 645–653.
  53. Mehmood, S.; Imran, M.; Ali, A.; Munawar, A.; Khaliq, B.; Anwar, F.; Saaed, Q.; Buck, F.; Hussain, S.; Saeed, A.; et al. Model prediction of a Kunitz-type trypsin inhibitor protein from seeds of Acacia nilotica L. with strong antimicrobial and insecticidal activity. Turk. J. Biol. 2020, 44, 188–200.
  54. Cai, X.; Xie, X.; Fu, N.; Wang, S. Physico-Chemical and Antifungal Properties of a Trypsin Inhibitor from the Roots of Pseudostellaria heterophylla. Molecules 2018, 23, 2388.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Maria Luiza Vilela Oliva
,
Camila Bonturi
,
Ana Beatriz Teixeira
,
,
Penélope Valente
,
Clovis Macêdo Bezerra Filho
,
Isabel Batista
View Times: 657
Revisions: 2 times (View History)
Update Date: 13 May 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback