Fibrinogen-clotting enzyme, pictobin, from Bothrops pictus snake venom. Structural and functional characterization

Clinical and Evolutionary Implications of Dynamic Coagulotoxicity Divergences in Bothrops (Lancehead Pit Viper) Venoms

“…Interestingly, despite being anticoagulant on human plasma, when tested on isolated fibrinogen, B. pictus venom induced a weak clot (A = 3.1 ± 0.1 mm) after an extended period (R = 1066.7 ± 23.6) ( Figure 3 ). This indicates that pseudo-procoagulant (aka ‘thrombin-like’) enzymes are present in the venom, which confirms previous studies [ 84 ]. When injected into prey items, the pseudo-procoagulant enzymes likely act synergistically with other anticoagulant toxins, consuming clotting factors to produce an anticoagulant pathology.…”

Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and Metabolic Plasticity of Cancer Cells During Metastasis

“…Interestingly, several toxins isolated from snake venom exhibit selective migrastatic effects in cancer cells by interaction with integrin receptors, alterations in the actin/cytoskeleton network, and EMT inhibition ( Urra and Araya-Maturana, 2017 , 2020 ). The recently identified snake toxin pictobin induces mitochondrial fragmentation and dysfunction ( Table 1 ), inhibiting the migration in cancer cells at non-cytotoxic concentrations ( Vivas-Ruiz et al, 2020 ). In analogy to the effects of human thrombin on mitochondrial metabolism in platelets ( Ravi et al, 2015 ), pictobin-induced mitochondrial dysfunction may be triggered by intracellular signaling initiated in the plasma membrane by cleavage of some receptor in cancer cells ( Vivas-Ruiz et al, 2020 ).…”

“…The recently identified snake toxin pictobin induces mitochondrial fragmentation and dysfunction ( Table 1 ), inhibiting the migration in cancer cells at non-cytotoxic concentrations ( Vivas-Ruiz et al, 2020 ). In analogy to the effects of human thrombin on mitochondrial metabolism in platelets ( Ravi et al, 2015 ), pictobin-induced mitochondrial dysfunction may be triggered by intracellular signaling initiated in the plasma membrane by cleavage of some receptor in cancer cells ( Vivas-Ruiz et al, 2020 ). Taking these selected examples, mitochondrial fragmentation, and bioenergetics inhibition may represent an attractive mechanism for new anti-metastatic approaches that interfere with the extracellular cues-metabolism communication.…”

A Novel Fast and Efficient Approach to Purify the Thrombin-like Enzyme from Two <i>Bothrops</i>-genus Snake Venoms

“…Among these, a group of serine proteinases enzymes convert fibrinogen into fibrin by cleaving fibrinopeptides A and/or B. As this activity resembles the activity of thrombin, these venom components are commonly named "thrombin-like" enzymes (SVTLEs) [41,43]. These proteins are good tools to study molecular details of activation of specific factors involved in coagulation and fibrinolytic cascades.…”

“…Bothrops snakes have their venom richly comnposed of SVTLE, several of which have already been purified and characterized: B. atrox [45], B. alternatus [11], B. pauloensis [10], B. moojeni [4], B. jararacussu [19], B. jararaca [42], B. brazili [46] and recently B. pictus [43]. The isolation of SVTLEs is of great interest to the scientific community due to the possibility of their use in the treatment of thrombotic diseases and as anticoagulants, in addition to their relevance as a target for the bioprospecting of new products [25].…”