Prothrombin activators are an important group of procoagulant (inducing blood clotting) proteins isolated from snake venom. Our contributions to this group of proteins are as follows.

• We purified, characterized and completed the amino acid sequence of snake venom prothrombin activators (group D) that are structurally and functionally similar to mammalian blood coagulation factor Xa. Its procoagulant properties and its substrate specificity can be exploited and hence we have applied for the provisional patent protection for this group of proteins isolated from venoms.  This is licensed to an Australian company.

• We have examined the structure-function relationships of group D prothrombin activators. Based on their structure and affinity to bovine factor Va, we developed new class of anticoagulant peptides that interfere in the interaction between factor Xa and factor Va and inhibit the formation of the prothrombinase complex (Patents pending).

• We have shown that group C prothrombin activators are similar to mammalian factor Xa-Va complex.  We have completed sequence of the enzymatic and non-enzymatic subunits, which are similar to factor Xa and factor Va respectively.

• We have shown that some Australian snakes have two parallel prothrombin activator systems: one expressed in their venom gland which they use as an offensive weapon in catching the prey and the other expressed in their liver which is a hemostatic factor that is important for their survival.

• We identified an intermediate in the evolution of the factor Xa-like enzymatic subunit of prothrombin activators.

• To understand the site-specific expression and regulation of expression, we completed the gene structures of both venom gland liver proteins. We described the duplication of factor X gene and recruitment into the venom gland.

 

 

Key Publications