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Veena S. Rao, R. Manjunatha Kini
Pseutarin C, a Prothrombin Activator from Pseudonaja textilis Venom: Its Structural and Functional Similarity to Mammalian Coagulation Factor Xa-Va Complex
Several snake venoms contain procoagulant proteins that can activate prothrombin. We have purified pseutarin C, a prothrombin activator from the venom of the Australian brown snake (Pseudonaja textilis). It converts prothrombin to thrombin by cleaving both the peptide bonds Arg274-Thr275 and Arg323-Ile324, similar to mammalian factor Xa. It is a protein complex (250 Kd) consisting of an enzymatic and a non- enzymatic subunit. These subunits were separated by reverse phase HPLC and their interactions with bovine factor Xa and factor Va were studied. The enzymatic subunit of pseutarin C has a 13 fold higher affinity for bovine factor Va (Kd of 11.4 nM for pseutarin C nzymatic subunit bovine factor Va interaction as compared to a Kd of 147.4 nM for the bovine factor Xa-Va interaction). The non-enzymatic component, however, was unable to activate bovine factor Xa. N-terminal sequence analysis of the catalytic subunit of pseutarin C showed 60% homology to mammalian factor Xa and 78% homology to trocarin, a group D prothrombin activator from Tropidechis carinatus venom. Structural information for the non-enzymatic subunit of pseutarin C was obtained by amino terminal sequencing of several internal peptides. The sequence data obtained indicates that the non-enzymatic subunit of pseutarin C has similar domain architecture like the mammalian factor Va and the overall homology is 55%. Thus pseutarin C is the first venom procoagulant protein that is structurally and functionally similar to mammalian factor Xa-Va complex.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 88, 01/2002
Pages: 611 - 619