Separation and Partial Characterization of a Coagulant Enzyme from <i>Bitis gabonica</i> Venom

Marsh, Neville; Whaler, B. C.

doi:10.1111/j.1365-2141.1974.tb00474.x

Cited by 38 publications

(6 citation statements)

References 15 publications

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“…Three serine protease containing fractions (E I to E III) isolated from B. gabonica venom have showed kinin releasing activity (E I), very low kinin releasing and high fibrinolytic activities (E II) and low clotting activity (E III) [10]. Marsh et al [26] reported two thrombin-like enzymes from B. gabonica venom, one with rapid defibrinating activity and another with a weak defibrinating activity. Some VVSPs from other snakes have been found to have two functions, for example crotalase has both kininogenase and fibrinogenolytic activities [22], and jararacussin [27], habu [28] and kangshuanmeni [29] are examples of serine proteases which have both α and β fibrinogenolytic activities.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to understand that the effects of VVSPs occur in the context of the functional activities of other potent biological venom components including other serine proteases, metalloproteases and phospholipases. Marsh et al [26] reported that the venom of B. gabonica causes rapid defibrination together with widespread haemorrhage, cardiac and pulmonary damage. Rhinocerase does not catalyse plasma clot formation but hydrolyses fibrinogen.…”

Section: Discussionmentioning

confidence: 99%

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Purification and Functional Characterisation of Rhinocerase, a Novel Serine Protease from the Venom of Bitis gabonica rhinoceros

et al. 2010

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BackgroundSerine proteases are a major component of viper venoms and are thought to disrupt several distinct elements of the blood coagulation system of envenomed victims. A detailed understanding of the functions of these enzymes is important both for acquiring a fuller understanding of the pathology of envenoming and because these venom proteins have shown potential in treating blood coagulation disorders.Methodology/Principal FindingsIn this study a novel, highly abundant serine protease, which we have named rhinocerase, has been isolated and characterised from the venom of Bitis gabonica rhinoceros using liquid phase isoelectric focusing and gel filtration. Like many viper venom serine proteases, this enzyme is glycosylated; the estimated molecular mass of the native enzyme is approximately 36kDa, which reduces to 31kDa after deglycosylation. The partial amino acid sequence shows similarity to other viper venom serine proteases, but is clearly distinct from the sequence of the only other sequenced serine protease from Bitis gabonica. Other viper venom serine proteases have been shown to exert distinct biological effects, and our preliminary functional characterization of rhinocerase suggest it to be multifunctional. It is capable of degrading α and β chains of fibrinogen, dissolving plasma clots and of hydrolysing a kallikrein substrate.Conclusions/SignificanceA novel multifunctional viper venom serine protease has been isolated and characterised. The activities of the enzyme are consistent with the known in vivo effects of Bitis gabonica envenoming, including bleeding disorders, clotting disorders and hypotension. This study will form the basis for future research to understand the mechanisms of serine protease action, and examine the potential for rhinocerase to be used clinically to reduce the risk of human haemostatic disorders such as heart attacks and strokes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Purification and Functional Characterisation of Rhinocerase, a Novel Serine Protease from the Venom of Bitis gabonica rhinoceros

et al. 2010

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“…The two independent lineages of giant Bitis are the most widespread and medically significant of the Bitis species due to their distribution, abundance in farmland, and extremely large venom yields. The most well studied species ( B. arietans , B. gabonica and B. rhinoceros ) have been studied in-depth due to the potent anticoagulant and hemorrhagic effects of their venom, being responsible for a significant proportion of the mortality and morbidity of snakebites in Africa [4,5,30,33,34]. The venom of both lineages of giant Bitis species causes a variety of effects including spontaneous and persistent bleeding, incoagulable blood, hemorrhage, hypotension and rapid defibrinogenation [30,31,32,33].…”

Section: Introductionmentioning

confidence: 99%

Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis

Youngman

Debono

Dobson

et al. 2019

Toxins

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The genus Bitis comprises 17 snake species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor of the clade consisting of B. gabonica, B. nasicornis, B. parviocula and B. rhinoceros) induce an array of debilitating effects including anticoagulation, hemorrhagic shock and cytotoxicity, whilst the dwarf species B. atropos is known to have strong neurotoxic effects. However, the venom effects of the other species within the genus have not been explored in detail. A series of coagulation assays were implemented to assess the coagulotoxic venom effects of fourteen species within the genus. This study identified procoagulant venom as the ancestral condition, retained only by the basal dwarf species B. worthingtoni, suggesting anticoagulant venom is a derived trait within the Bitis genus and has been secondarily amplified on at least four occasions. A wide range of anticoagulant mechanisms were identified, such as coagulant and destructive activities upon fibrinogen in both giant and dwarf Bitis and the action of inhibiting the prothrombinase complex, which is present in a clade of dwarf Bitis. Antivenom studies revealed that while the procoagulant effects of B. worthingtoni were poorly neutralized, and thus a cause for concern, the differential mechanisms of anticoagulation in other species were all well neutralized. Thus, this study concludes there is a wide range of coagulotoxic mechanisms which have evolved within the Bitis genus and that clinical management strategies are limited for the procoagulant effects of B. worthingtoni, but that anticoagulant effects of other species are readily treated by the South African polyvalent antivenom. These results therefore have direct, real-work implications for the treatment of envenomed patients.

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“…The characterization of the effects of rhinocetin on a range of collagen-induced (integrin α2β1-dependent) platelet functions such as inside-out signaling, calcium release, granule secretion, and thrombus formation greatly improves our understanding of this group of viper snaclecs. In a clinical context, rhinocetin inhibition of platelet function is consistent with the bleeding pathology that follows systemic envenoming by gaboon vipers (48). …”

Section: Discussionmentioning

confidence: 74%

Rhinocetin, a Venom-derived Integrin-specific Antagonist Inhibits Collagen-induced Platelet and Endothelial Cell Functions

Vaiyapuri

Hutchinson

Ali

et al. 2012

Journal of Biological Chemistry

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Background: Snaclecs affect the hemostasis of snakebite victims upon envenomation. Results: Rhinocetin, a novel snaclec, inhibits integrin α2β1-dependent functions of human platelets and endothelial cells. Conclusion: The actions of rhinocetin are consistent with hemorrhagic symptoms upon envenomation. Significance: Due to its inhibitory actions on integrin α2β1, rhinocetin may have potential diagnostic and therapeutic values.

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Separation and Partial Characterization of a Coagulant Enzyme from Bitis gabonica Venom

Cited by 38 publications

References 15 publications

Purification and Functional Characterisation of Rhinocerase, a Novel Serine Protease from the Venom of Bitis gabonica rhinoceros

Purification and Functional Characterisation of Rhinocerase, a Novel Serine Protease from the Venom of Bitis gabonica rhinoceros

Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis

Rhinocetin, a Venom-derived Integrin-specific Antagonist Inhibits Collagen-induced Platelet and Endothelial Cell Functions

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