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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-12-3839.
Submitted December 19, 2002
Accepted April 7, 2003
The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V
Veena S Rao, Sanjay Swarup, and R Manjunatha Kini*
Department of Biological Sciences, National University of Singapore, Singapore; Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA
* Corresponding author; email: dbskinim{at}nus.edu.sg.
Pseutarin C is a group C prothrombin activator from the venom of the eastern brown snake Pseudonaja textilis. It is a multi-subunit protein complex consisting of catalytic and nonenzymatic subunits similar to coagulation factor Xa and factor Va, respectively. Here we describe the complete sequence of the nonenzymatic subunit. Based on the partial amino acid sequence of the nonenzymatic subunit degenerate primers were designed. Using a "walking" strategy based on sequentially designed primers, we determined the complete cDNA sequence of the nonenzymatic subunit. The cDNA encodes a protein of 1461 amino acid residues, which includes a 30-residue signal peptide, a mature protein of 1430 amino acid residues and a stop codon. cDNA blot analysis showed a single transcript of ~ 4.6 kb. The deduced amino acid sequence shows ~50% identity to mammalian factor V and by homology has a similar domain structure consisting of domains A1-A2-B-A3-C1-C2. Interestingly, the B domain of pseutarin C is shorter than that of mammalian FV. Although, most of the proteolytic activation sites are conserved, two of the three proteolytic sites cleaved by activated protein C are mutated and thus activated protein C is not able to inactivate this procoagulant toxin. The predicted post-translational modifications, including disulfide bonds, N-glycosylation, phosphorylation and sulfation, in pseutarin C are significantly different compared to bovine factor V. Thus our data demonstrates that the nonenzymatic subunit of group C prothrombin activators is structurally similar to mammalian FV.
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