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Bothrojaracin – A Potent Thrombin Inhibitor

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Toxins and Hemostasis

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Abstract

Snake venoms are rich in a large variety of proteins and peptides that can interfere with the hemostatic system. This review focuses on bothrojaracin, which is snaclec molecule, either bind to thrombin, inhibiting its biological activities, such as clotting of fibrinogen, platelet activation or to prothrombin, impairing thrombin formation. Bothrojaracin interacts with both molecules, forming a stable 1:1 complex. The calculated Kd for bothrojaracin was 0.6 nM and 100 nM for thrombin and prothrombin, respectively. Bothrojaracin binds to thrombin exosite I displacing ligands such as fibrin, hirudin, thrombomodulin and factor V and do not block the catalytic site. This protein has helped in our understanding of some molecular aspects of the thrombin and prothrombin structure–function relationship. The knowledge about the mechanism of action and details of structural aspects will certainly result in new medical and pharmacological applications. Furthermore, bothrojaracin offer attractive template for the development of rationally designed therapeutic agents.

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  1. Instituto de Bioquímica Medica, Centro de Ciências da Saúde, UFRJ, Rio de Janeiro, Brazil

    Russolina B. Zingali & Ana Cristina Ferraz Nogueira

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  1. Russolina B. Zingali
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  2. Ana Cristina Ferraz Nogueira
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Correspondence to Russolina B. Zingali .

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  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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© 2010 Springer Science+Business Media B.V.

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Zingali, R.B., Nogueira, A.C.F. (2010). Bothrojaracin – A Potent Thrombin Inhibitor. 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_12

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