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Anticoagulant Phospholipases A2 Which Bind to the Specific Soluble Receptor Coagulation Factor Xa

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Toxins and Hemostasis

Abstract

This review will focus on Viperidae venom secreted Phospholipases A2 (sPLA2s) that exert an anticoagulant effect by a non-enzymatic, phospholipid-independent mechanism through direct binding to human coagulation factor Xa (FXa). We present the potential FXa-binding site of these anticoagulant PLA2s and the potential PLA2-binding site of FXa based on molecular docking calculations, site-directed mutagenesis and SPR affinity binding studies. We also discuss the structures of recently crystallized natural isoforms of PLA2 which interact with FXa with different affinity and which differ in anticoagulant activity. The three-dimensional structure of the PLA2 isoforms helps to explain the role of natural mutations in the binding mode of PLA2 with FXa and will be useful in structure-based design of non-competitive FXa inhibitors as potential new anticoagulant drugs.

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Authors and Affiliations

  1. Département de Biologie Structurale et Chimie, Institut Pasteur, Unité d’Immunologie Structurale; CNRS, URA 2185, F-75015, Paris, France

    Grazyna Faure, Haijin Xu & Frederick Saul

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  1. Grazyna Faure
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  2. Haijin Xu
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  3. Frederick Saul
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Correspondence to Grazyna Faure .

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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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Faure, G., Xu, H., Saul, F. (2010). Anticoagulant Phospholipases A2 Which Bind to the Specific Soluble Receptor Coagulation Factor Xa. 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_13

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