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Blood coagulation is a highly synchronized event of sequential activation reactions of several coagulation factors, and prothrombin activation is in the center of this cascade. In the physiological system, activated coagulation factor X (FXa) forms a complex (prothrombinase complex) with factor Va, Ca 2+ , and phospholipids and converts prothrombin to thrombin. Several exogenous prothrombin activators, particularly groups C and D from the Australian snake venoms, also activate prothrombin in a similar fashion. Recent studies have shown that they are structurally and functionally similar to the blood coagulation factors. Group C prothrombin activators resemble FVa-FXa complex, whereas group D prothrombin activators are similar to FXa. Thus, these snakes possess two parallel prothrombin activating systems, one in their venom and the other in their blood. These closely related proteins have distinctly different physiological roles. In this review, we will discuss the structural characteristics and evolution of the venom prothrombin activators and blood coagulation factors from Australian elapids. [ABSTRACT FROM AUTHOR]

Background: Toxin profiling helps in cataloguing the toxin present in the venom as well as in searching for novel toxins. The former helps in understanding potential pharmacological profile of the venom and evolution of toxins, while the latter contributes to understanding of novel mechanisms of toxicity and provide new research tools or prototypes of therapeutic agents., Results: The pygmy copperhead (Austrelaps labialis) is one of the less studied species. In this present study, an attempt has been made to describe the toxin profile of A. labialis from Kangaroo Island using the cDNA library of its venom glands. We sequenced 658 clones which represent the common families of toxin genes present in snake venom. They include (a) putative long-chain and short-chain neurotoxins, (b) phospholipase A2, (c) Kunitz-type protease inhibitor, (d) CRISPs, (e) C-type lectins and (f) Metalloproteases. In addition, we have also identified a novel protein with two Kunitz-type domains in tandem similar to bikunin., Conclusion: Interestingly, the cDNA library reveals that most of the toxin families (17 out of 43 toxin genes; approximately 40%) have truncated transcripts due to insertion or deletion of nucleotides. These truncated products might not be functionally active proteins. However, cellular transcripts from the same venom glands are not affected. This unusual higher rate of deletion and insertion of nucleotide in toxin genes may be responsible for the lower toxicity of A. labialis venom of Kangroo Island and have significant effect on evolution of toxin genes.

1. Snake venoms are complex mixtures of pharmacologically active peptides and proteins. 2. These protein toxins belong to a small number of superfamilies of proteins. The present review describes structure-function relationships of three-finger toxins. 3. All toxins share a common structure of three beta-stranded loops extending from a central core. However, they bind to different receptors/acceptors and exhibit a wide variety of biological effects. 4. Thus, the structure-function relationships of this group of toxins are complicated and challenging. 5. Studies have shown that the functional sites in these "sibling" toxins are located on various segments of the molecular surface.