Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom

Sartim, Marco A.; Pinheiro, Matheus Pinto; Pádua, Ricardo Augusto Pereira de; Sampaio, Suely Vilela; Nonato, Maria Cristina

doi:10.1016/j.toxicon.2016.12.007

Cited by 7 publications

(9 citation statements)

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“…Their abundance in venoms is in the range of 1–2% [25], but can reach 4–8% [23]. The crystal structure of the galactose-binding rattle snake lectin (RSL) from Crotalus atrox was the first to be resolved in 2004 [30], followed by the structure of the Bothrops jararacussu galactose-binding lectin (BjcuL) [31]. Based on their homologies, corresponding snake venom lectins from various other Viperidae and from Elapidae species, e.g., from Bungarus fasciatus , were structurally modelled [32] and revealed characteristic features.…”

Section: Sugar-binding C-type Lectins From Snake Venomsmentioning

confidence: 99%

Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

Eble

2019

Toxins

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Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca2+- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share the robust C-type lectin domain (CTLD) fold but differ in a long loop, which either contributes to a sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. Most C-type lectin (-related) proteins assemble in ordered supramolecular complexes with a high versatility of subunit numbers and geometric arrays. Similarly versatile is their ability to inhibit or block their target molecules as well as to agonistically stimulate or antagonistically blunt a cellular reaction triggered by their target receptor. By utilizing distinct interaction sites differentially, SV-CLRPs target a plethora of molecules, such as distinct coagulation factors and receptors of platelets and endothelial cells that are involved in hemostasis, thrombus formation, inflammation and hematogenous metastasis. Because of their robust structure and their high affinity towards their clinically relevant targets, SV-CLRPs are and will potentially be valuable prototypes to develop new diagnostic and therapeutic tools in medicine, provided that the molecular mechanisms underlying their versatility are disclosed.

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Section: Sugar-binding C-type Lectins From Snake Venomsmentioning

confidence: 99%

Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

Eble

2019

Toxins

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“…Thermofluor assays present several applications, and they can be very useful in toxinology in order to evaluate the purification procedure and storage protocols, also helping to optimize these protocols [46,47]. Moojase showed the highest ∆Tm at pH 5.5, with increasing thermostability in the presence of sodium chloride up to 1 M. This could be associated with the salting-in phenomenon, considering that thermostability and solubility can have a positive correlation [48,49].…”

Section: Discussionmentioning

confidence: 99%

“…The thermostability of Moojase was also assessed by the thermofluor assay. This approach evaluates the effects of temperature-dependent protein unfolding by measuring the protein melting temperature (Tm) [47,62]. Moojase was screened for several solutions with different buffers, pH, and ionic strength formulations that promote protein solubility and stability.…”

Section: Methodsmentioning

confidence: 99%

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New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom

Amorim

Menaldo

Carone

et al. 2018

Toxins

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Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs. Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom. The toxin was isolated from the crude venom using a two-step chromatographic procedure. Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80–6.88). Sequencing of Moojase indicated that it is an isoform of Batroxobin. Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties. Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA. RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa. Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures. Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.

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“…It has a carbohydrate binding specificity for β-galactose, belonging to the C-type lectin with calcium binding zone. The crystallographic structure of BJcuL has been resolved, which reveals a porous and flexible decameric conformation composed of five dimers [ 47 ]. BJcuL is able to interact with glycoligands targets on the surface of gastric carcinoma cells MKN45 and AGS, and decrease their viability and adhesion, at last result in cytotoxic effects [ 48 ].…”

Section: Anti-cancer Mechanism Of Venom Peptidesmentioning

confidence: 99%

Venom-based peptide therapy: insights into anti-cancer mechanism

Mahadevappa

Kwok

2017

Oncotarget

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The 5-year relative survival rate of all types of cancer has increased significantly over the past three decades partly due to the targeted therapy. However, still there are many targeted therapy drugs could play a role only in a portion of cancer patients with specific molecular alternation. It is necessary to continue to develop new biological agents which could be used alone and/or in combination with current FDA approved drugs to treat complex cancer diseases. Venom-based drugs have been used for hundreds of years in human history. Nevertheless, the venom-origin of the anti-cancer drug do rarely appear in the pharmaceutical market; and this is due to the fact that the mechanism of action for a large number of the venom drug such as venom-based peptide is not clearly understood. In this review, we focus on discussing some identified venom-based peptides and their anti-cancer mechanisms including the blockade of cancer cell proliferation, invasion, angiogenesis, and metastasis (hallmarks of cancer) to fulfill the gap which is hindering their use in cancer therapy. Furthermore, it also highlights the importance of immunotherapy based on venom peptide. Overall, this review provides readers for further understanding the mechanism of venom peptide and elaborates on the need to explore peptide-based therapeutic strategies.

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Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom

Cited by 7 publications

References 50 publications

Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

Structurally Robust and Functionally Highly Versatile—C-Type Lectin (-Related) Proteins in Snake Venoms

New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom

Venom-based peptide therapy: insights into anti-cancer mechanism

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