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Thromb Haemost 2002; 88(04): 611-619
DOI: 10.1055/s-0037-1613264
Review Article
Schattauer GmbH

Pseutarin C, a Prothrombin Activator from Pseudonaja textilis Venom: Its Structural and Functional Similarity to Mammalian Coagulation Factor Xa-Va Complex

Veena S. Rao
1   Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Republic of Singapore
,
R. Manjunatha Kini
1   Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Republic of Singapore
› Author Affiliations
Further Information

Publication History

Received 11 February 2002

Accepted after resubmission 28 May 2002

Publication Date:
09 December 2017 (online)

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Summary

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 nonenzymatic 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 (K d of 11.4 nM for pseutarin C enzymatic subunit – bovine factor Va interaction as compared to a K d 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.

Keywords

Prothrombinase complex - eastern brown snake - blood coagulation - thrombin formation - procoagulant toxin
 

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