Trocarin, a blood coagulation factor Xa homologue from snake venom, causes inflammation and mitogenesis

Joseph, Jeremiah S.; Thirumangalathu, Shoba; Tsang, Fai; Wong, W.S. Fred; Kini, R. Manjunatha

doi:10.1016/j.toxicon.2003.10.020

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…Six of the putative platypus venom serine proteases were found to have homology to endogenous coagulation factors (for example, Factor X), which are involved in the blood coagulation cascade, and snake venom group D prothrombin activators such as trocarin D, which cause coagulation and inflammation [35]. Many other proteins encoded by genes identified in the platypus venom transcriptome also appear to have hemostatic effects (Table 1), as do many snake venoms [36].…”

Section: Resultsmentioning

confidence: 99%

Novel venom gene discovery in the platypus

et al. 2010

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BackgroundTo date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components.ResultsWe identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation.ConclusionsThis study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom.

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Section: Resultsmentioning

confidence: 99%

Novel venom gene discovery in the platypus

et al. 2010

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“…The PLA 2 from snake venom is a potent mediator of edema (5,24). The edema-inducing effects of ecarpholin S were measured in mice, as described earlier (25). Different doses of ecarpholin S were dissolved in 20 mL of PBS (pH 7.5) and administered via subplantar injection into the left footpad of Swiss albino mice under anesthesia.…”

Section: Edema-inducing Activitymentioning

confidence: 99%

Structural Characterization of Myotoxic Ecarpholin S From Echis carinatus Venom

Zhou

Tan

Valiyaveettil

et al. 2008

Biophysical Journal

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Phospholipase A(2) (PLA(2)), a common toxic component of snake venom, has been implicated in various pharmacological effects. Ecarpholin S, isolated from the venom of the snake Echis carinatus sochureki, is a phospholipase A(2) (PLA(2)) belonging to the Ser(49)-PLA(2) subgroup. It has been characterized as having low enzymatic but potent myotoxic activities. The crystal structures of native ecarpholin S and its complexes with lauric acid, and its inhibitor suramin, were elucidated. This is the first report of the structure of a member of the Ser(49)-PLA(2) subgroup. We also examined interactions of ecarpholin S with phosphatidylglycerol and lauric acid, using surface plasmon resonance, and of suramin with isothermal titration calorimetry. Most Ca(2+)-dependent PLA(2) enzymes have Asp in position 49, which plays a crucial role in Ca(2+) binding. The three-dimensional structure of ecarpholin S reveals a unique conformation of the Ca(2+)-binding loop that is not favorable for Ca(2+) coordination. Furthermore, the endogenously bound fatty acid (lauric acid) in the hydrophobic channel may also interrupt the catalytic cycle. These two observations may account for the low enzymatic activity of ecarpholin S, despite full retention of the catalytic machinery. These observations may also be applicable to other non-Asp(49)-PLA(2) enzymes. The interaction of suramin in its complex with ecarpholin S is quite different from that reported for the Lys(49)-PLA(2)/suramin complex(,) where the interfacial recognition face (i-face), C-terminal region, and N-terminal region of ecarpholin S play important roles. This study provides significant structural and functional insights into the myotoxic activity of ecarpholin S and, in general, of non-Asp(49)-PLA(2) enzymes.

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“…Recent studies have shown that group C and D prothrombin activators from snake venoms are structurally and functionally similar to the mammalian blood coagulation factor (F)Xa-FVa complex and FXa, respectively [1][2][3]. These venom proteins induce disseminated vascular coagulopathy, cyanosis and death and thus are used as toxins by the snakes [4,5]. As vertebrates, snakes also have their own hemostatic system to prevent excessive blood loss resulting from injuries [6,7].…”

Section: Introductionmentioning

confidence: 99%

Structure of two genes encoding parallel prothrombin activators in Tropidechis carinatus snake: gene duplication and recruitment of factor X gene to the venom gland

Reza

Swarup

Kini

2007

Journal of Thrombosis and Haemostasis

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To cite this article: Reza MA, Swarup S, Kini RM. Structure of two genes encoding parallel prothrombin activators in Tropidechis carinatus snake: gene duplication and recruitment of factor X gene to the venom gland J Thromb Haemost 2007; 5: 117-26.Summary. Background: Proteins with new function originate through gene duplication followed by divergence. In nature, occurrence of structurally and functionally similar proteins performing highly diverse physiological roles within an organism is rare. Several Australian elapid snakes have two parallel prothrombin activating systems with distinct physiological roles. For example, in Tropidechis carinatus, trocarin D exists in the venom and acts as toxin, whereas coagulation factor (F) X exists in plasma and plays a role in hemostasis. Results: Here, we show that FX and the trocarin D genes are expressed in a highly tissue-specific manner in T. carinatus. To understand their origin, recruitment and evolution, we determined the complete structure of their genes. Both genes have eight exons with identical exon-intron boundaries. All the introns are 92-99% identical with the exception of intron 1, indicating a recent gene duplication event. The first intron of the trocarin D gene is also nearly identical to that of the FX gene, except for two deletions (255 and 1406 bp) and three insertions (214, 1975, and 2174 bp). The third insertion has a potential scaffold/matrix attached region. The putative promoter of the snake FX gene shares similar cis-elements compared with those of human and murine FX genes. Interestingly, the trocarin D promoter has a 264-bp insertion with core promoter sequences and cis-elements that are known to induce high-level expression. This insertion might be responsible for switching from constitutive expression of the FX gene to inducible expression of trocarin D. Thus, we named this segment as VERSE (Venom Recruitment/Switch Element). Conclusion: To our knowledge, this is the first molecular evidence for the recruitment of a duplicated gene for expression in venom glands by a simple insertion.

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Trocarin, a blood coagulation factor Xa homologue from snake venom, causes inflammation and mitogenesis

Cited by 12 publications

References 35 publications

Novel venom gene discovery in the platypus

Novel venom gene discovery in the platypus

Structural Characterization of Myotoxic Ecarpholin S From Echis carinatus Venom

Structure of two genes encoding parallel prothrombin activators in Tropidechis carinatus snake: gene duplication and recruitment of factor X gene to the venom gland

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