Toxins in thrombosis and haemostasis: potential beyond imagination

Authors

  • R. M. KINI

    1. Protein Science Laboratory, Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore
    2. Department of Biochemistry and Molecular Biology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA
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R. Manjunatha Kini, Protein Science Laboratory, Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
Tel.: +65 6516 5235; fax: +65 6779 2486.
E-mail: dbskinim@nus.edu.sg

Abstract

Summary.  Exogenous factors isolated from venoms of snakes and saliva of haematophagous animals that affect thrombosis and haemostasis have contributed significantly to the development of diagnostic agents, research tools and life-saving drugs. Here, I discuss recent advances in the discovery, structural and functional characterisation, and mechanism of action of new procoagulant and anti-haemostatic proteins. In nature, these factors have evolved to target crucial ‘bottlenecks’ in the coagulation cascade and platelet aggregation. Several simple protein scaffolds are used to target a wide variety of target proteins and receptors exhibiting functional divergence. Different protein scaffolds have also evolved to target identical, physiologically relevant key enzymes or receptors exhibiting functional convergence. At times, exogenous factors bind to the same target protein, but at distinct sites, to differentially attenuate their functions exhibiting mechanistic divergence within the same family of proteins. The structure-function relationships of these factors are subtle and complicated but represent an exciting challenge. These studies provide ample opportunities to design highly specific and precise ligands to achieve desired biological target function. Although only a small number of them have been characterised to date, the molecular and mechanical diversities of these exogenous factors and their contributions to understanding molecular and cellular events in thrombosis and haemostasis as well as developing diagnostic and research tools and therapeutic agents, is outstanding. Based on the current status, I have attempted to identify future potential and prospects in this area of research.

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