Australian snake venoms
Snake venoms contain a complex cocktail of toxic components. Whereas research on non-Australian snake venoms has been intensive with several major toxin classes being characterised at the molecular level, Australian snake toxin research is in its infancy. So far only three toxin classes have been identified: procoagulants (prothrombin activators), phospholipase A2s (PLA2s), and neurotoxins. Thus Australian snake venoms remain largely an untapped resource. Moreover, few researchers in Australia have taken up the challenge with the result that of the 35 Australian snake toxins with complete amino acid sequences identified to date 28 have been by overseas researchers.
Procoagulants
Most procoagulants are prothrombin activating enzymes and are multisubunit complexes of 50-70 kDa or greater than 200 kDa. None have been fully characterised at the molecular level. Procoagulants lead to disseminated intravascular coagulation with defibrination with the net effect being hypo-coagulable blood.
The use of these activators are well documented and they are to diagnose dysprothrombin aemias, to determine prothrombin concentration, and are excellent tools to activate prothrombin to thrombin. They are also useful in activating descarboxyprothrombin. A recent use is to make FDA approved fibrin film for sugical procedures, Taipan activator is used to activate recombinant prethrombin to alpha thrombin.An extremely interesting, and useful, aspect of venom components from Australian elapids is in the characterisation of lupus using the procoagulant textarin from the eastern brown snake (Pseudonaja textilis). Lupus anticoagulants (LA) are secretory IgA, or serum IgG and IgM, immunoglobins which characteristically interfere with phospholipid dependent in vitro coagulation tests. A sensitive and rather specific confirmatory test has been developed using textarin in conjunction with ecarin from the saw-scaled viper (Echis carinatus). In the presense of LA the activation time of prothrombin by textarin is prolonged but that of ecarin is unaffected, thus the test consists of a useful comparative ratio between textarin/ecarin.
Phospholipase A2s and related molecules
Phospholipase A2s are the best studied toxin class with approximately 150 protein sequences determined worldwide. They typically contain 118 residues with 7 conserved disulfide bonds and present a similar well defined tertiary fold. Six general classes of PLA2s from Australian snake venoms have been identified. These typically exhibit two separate and independent actions: a non-lethal esterase activity and a toxic neurological activity where neurotoxic PLA2s act by pre- or post-synaptic blockade of neuromuscular nerve transmission. Most of the Australian PLA2 sequences described to date have come from 'the usual suspects' though less than half have been fully characterised. This is indeed unfortunate if a fuller understanding of the clinical pathology or their structure-function relationships is to be gleaned.
Neurotoxins
The neurotoxins found in Australian venomous snakes are the most potent of any snake neurotoxins in the world. Most neurotoxins found in Australian elapid venoms so far have a curare-like action and bind with high affinity to post-synaptic skeletal muscle nicotinic acetylcholine receptors. The individual toxins vary in size and disulfide bridging but maintain a similar tertiary fold. More specifically the short chain neurotoxins have a primary structure similar to the long chain neurotoxins but the long chains toxins have a C-terminal extension containing the fifth cysteine bond. A clear opportunity exists to expand our knowledge in this area.
See also: Poisonous snakes of Australia