Snake venom prothrombin activators homologous to blood coagulation factor Xa

Haemostasis
J S Joseph, R M Kini

Abstract

We have recently determined the complete amino acid sequence of trocarin, a group D prothrombin activator from the venom of Tropidechis carinatus (Australian rough-scaled snake). This proteinase is both functionally and structurally similar to mammalian blood coagulation factor Xa. It shows approximately 70% homology and possesses the characteristic Gla domain, two EGF domains and serine proteinase domain. To examine structure-function relationships, we generated a molecular model of trocarin based on a human factor Xa des-Gla crystal structure (1xka) as template. Based on known sites of interaction between mammalian factor Xa, factor Va and prothrombin, structure-function relationships of trocarin were explored. Unlike factor Xa, trocarin is glycosylated and has a large carbohydrate moiety at the entrance to its active site pocket. This might contribute to differences observed in the kinetics of hydrolysis of synthetic substrates by trocarin as compared to human factor Xa. A Ca(2+)-binding loop present in the heavy chain of factor Xa also seems to be lost in trocarin. In addition to its role in hemostasis, factor Xa shows other biological effects, including inflammation via its interaction with effector protease receptor-1 (EP...Continue Reading

Citations

Sep 25, 2012·Toxicon : Official Journal of the International Society on Toxinology·Francis S Markland, Stephen Swenson
Mar 27, 2010·Toxicon : Official Journal of the International Society on Toxinology·Geoffrey K IsbisterLisa F Lincz
Oct 30, 2008·Toxicon : Official Journal of the International Society on Toxinology·L P KernP Monagle
Feb 12, 2008·Toxicon : Official Journal of the International Society on Toxinology·Markus BergerJorge A Guimarães
Feb 27, 2007·Toxicon : Official Journal of the International Society on Toxinology·Linda Christian Carrijo-Carvalho, Ana Marisa Chudzinski-Tavassi
Jul 19, 2011·Toxicology and Applied Pharmacology·Yuling QiuByung Rae Jin
Nov 16, 2012·Toxicon : Official Journal of the International Society on Toxinology·Abhishek GulatiStephen B Duffull
Feb 24, 2007·Molecular & Cellular Proteomics : MCP·Geoff W BirrellMartin F Lavin
Jun 11, 2015·The Cochrane Database of Systematic Reviews·Kalana MaduwageGeoffrey K Isbister
Jul 25, 2014·The Journal of Toxicological Sciences·Azza M Abdel-Aty, Ahmed F Wahby

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