Thrombin pp 219-256 | Cite as

Hirudin Interactions with Thrombin

  • Stuart R. Stone
  • John M. Maraganore
Chapter

Abstract

Hirudin was originally isolated from the salivary glands of the medicinal leech Hirudo medicinalis. The anticoagulant activity of leech saliva was first described over 100 years ago by Haycraft (1884) and a polypeptide with antithrombin activity was first isolated over 30 years ago by Markwardt (1957). The amino acid sequence of the major form of hirudin was determined by Bagdy et al. (1976) and Dodt et al. (1984) (see also Mao et al., 1987) and is given in Fig. 1. The most striking feature of the amino acid sequence is the high proportion of acidic residues (12 out of 65); seven of these occur in the C-terminal region from residues 53 to 65, including the sulfated tyrosine residue at position 63 that is formed by postranslational modification. Hirudin contains six cysteines that form three disulfide bridges (h-Cys-6—Cys-14, h-Cys-16—Cys-28, and h-Cys-22—Cys-391) that were elucidated by Dodt et al. (1985) and are also shown in Fig. 1. Subsequently, more than 20 different isoforms of hirudin have been isolated from H. medicinalis and sequenced (Dodt et al., 1986; Harvey et al., 1986; Tripier, 1988; Scharf et al.,1989) and all of these forms seem to have antithrombin activity. All of the isoforms are highly homologous with levels of identity usually greater than 80%; the conserved residues are indicated in Fig. 1. The disulfide bridges and the acidic nature of the molecule, including the sulfated tyrosine, are invariant.

Keywords

Binding Energy Anticoagulant Activity Medicinal Leech Recombinant Hirudin Human Thrombin 
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Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Stuart R. Stone
    • 1
  • John M. Maraganore
    • 2
  1. 1.MRC CentreUniversity of CambridgeCambridgeUK
  2. 2.Biogen, Inc.CambridgeUSA

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