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Toxins and Hemostasis pp 447–464Cite as

Activation of Factor X by Snake Venom Proteases

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Abstract

Human coagulation factor X is a serine protease zymogen, which circulates in blood as a two-chain molecule. A variety of factor X activators have been detected in snake venoms. About 15 activators have been isolated from Viperidae, Crotalidae and Elapidae venoms. Viperidae and Crotalidae venom activators are mainly metalloproteases. Only two factor X activators are characterized from Elapidae venoms, both belonging to serine proteases. Most thoroughly investigated snake venom factor X activators are from Vipera russellii (now renamed Daboia russellii) - RVV-X, and Vipera lebetina (now renamed Macrovipera lebetina) - VLFXA. RVV-X is a heterotrimeric metalloproteinase with a mammalian ADAM-like heavy chain and two lectin-like light chains. The crystal structure of RVV-X has recently been determined. VLFXA is the first factor X activator that was cloned and sequenced and its primary structure was deduced from the cDNA sequences. Both activators consist of a heavy chain and two C-type lectin–like light chains which are held together by disulfide bonds. Heavy chains of RVV-X and VLFXA contain metalloprotease, disintegrin-like and cysteine-rich domains. All chains of VLFXA and RVV-X are synthesized from different genes. The primary structures of factor X activating snake venom serine proteases are unknown up to now.

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Acknowledgements

The work was financially supported by Estonian Science Foundation grant No. 7251 and by target financing SF0180114Bs08.

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Authors and Affiliations

  1. Laboratory of Bioorganic Chemistry, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, 12618, Estonia

    Jüri Siigur

  2. National Institute of Chemical Physics and Biophysics, Tallinn, 12618, Estonia

    Ene Siigur

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  1. Jüri Siigur
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Correspondence to Jüri Siigur .

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Editors and Affiliations

  1. , Department of Biological Sciences, National University of Singapore, Science Drive 4 14, Singapore, 117543, Singapore

    R. Manjunatha Kini

  2. , Department of Haematology, University of Berne, Inselspital, Bern, CH-3010, Switzerland

    Kenneth J Clemetson

  3. , Biochemistry and Molecular Biology, University of Southern California, Health Sciences Campus/9270, Los Angeles, 90089, USA

    Francis S. Markland

  4. , Medical Technology, University of Delaware, 305G Willard Hall Educ Bld, Newark, 19716, Delaware, USA

    Mary Ann McLane

  5. , Biochemistry, Meiji Pharmaceutical University, Nishio Kiyose 2-522-1, Tokyo, 204-8588, Japan

    Takashi Morita

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Siigur, J., Siigur, E. (2010). Activation of Factor X by Snake Venom Proteases. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_26

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