| Type: | Family | Name: | Proteinase inhibitor I15, leech antistasin |
| Description: | This group of serine protease inhibitors belong to MEROPS inhibitor family I15, clan IO. They inhibit serine peptidases of the S1 family () [] and are characterised by a well conserved pattern of cysteine residues. This is a family of leech anti-coagulants.Antistasin is a 15kDa protein found in the salivary glands of Haementeria officinalis(Mexican leech); it is an anticoagulant that functions by inhibiting factor Xa. The protein contains 119 residues, with an unusually high cysteine content (20 residues in all), and exhibits a 2-fold internal repeated structure. Four isoforms of antistasin have beenidentified in leech salivary gland extracts; partial sequence analysis indicates that these isoforms differ only by 1 or 2 amino acid residues [].Ghilanten is an anticoagulant-antimetastatic protein of Haementeria ghilianii(Amazon leech). Like antistasin, it contains 119 amino acids, with 20 cysteines, and a heparin-binding consensus motif at its C terminus.Arginine-34 is the residue involved in the active-site inhibition of trypsin and Factor Xa [].The 3D structure of antistasin has been determined to 1.9A resolution by X-ray crystallography []. The structure reveals a novel protein foldcomprising two similar domains, which can be divided into two similarly sized subdomains, with different relative orientations. Thus, the domainshapes differ, the N-terminal domain being wedge-shaped and the C-terminal domain flat []. Docking studies suggest that it is differences in domainshape that enable the N-terminal domain to bind and inhibit factor Xa, rather than the C-terminal domain, despite very similar active sites. A putative exosite binding region is evident in the N-terminal domain (residues 15-17), which is likely to interact with a cluster of positivelycharged residues on the factor Xa surface (Arg222/Lys223/Lys224), explaining the specificity and inhibitory potency of antistasin towards factor Xa. | Short Name: | Prot_inh_I15_antistasin_leech |
