Protein Domain : Proteinase inhibitor I15, leech antistasin IPR008086

Type	Family
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-foldinternal repeated structure. Four isoforms of antistasin have been identified 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 trypsinand Factor Xa [ ]. The 3D structure of antistasin has been determined to 1.9A resolution by X-ray crystallography [ ]. The structure reveals a novel protein fold comprising two similar domains, which can be divided into two similarly sized subdomains, with different relative orientations. Thus, the domain shapes differ, the N-terminal domain being wedge-shaped and the C-terminal domain flat []. Docking studies suggest that it is differences in domain shape 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 positively charged 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