1SKZ
PROTEASE INHIBITOR
Summary for 1SKZ
| Entry DOI | 10.2210/pdb1skz/pdb |
| Descriptor | ANTISTASIN, CHLORIDE ION (3 entities in total) |
| Functional Keywords | antistasin, factor xa inhibitor, serine protease inhibitor, thrombosis |
| Biological source | Haementeria officinalis (Mexican leech) |
| Cellular location | Secreted: P15358 |
| Total number of polymer chains | 1 |
| Total formula weight | 13411.15 |
| Authors | Krengel, U.,Dijkstra, B.W. (deposition date: 1997-04-16, release date: 1997-10-22, Last modification date: 2024-11-20) |
| Primary citation | Lapatto, R.,Krengel, U.,Schreuder, H.A.,Arkema, A.,de Boer, B.,Kalk, K.H.,Hol, W.G.,Grootenhuis, P.D.,Mulders, J.W.,Dijkema, R.,Theunissen, H.J.,Dijkstra, B.W. X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa. EMBO J., 16:5151-5161, 1997 Cited by PubMed Abstract: The three-dimensional structure of antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican leech Haementeria officinalis was determined at 1.9 A resolution by X-ray crystallography. The structure reveals a novel protein fold composed of two homologous domains, each resembling the structure of hirustasin, a related 55-residue protease inhibitor. However, hirustasin has a different overall shape than the individual antistasin domains, it contains four rather than two beta-strands, and does not inhibit factor Xa. The two antistasin domains can be subdivided into two similarly sized subdomains with different relative orientations. Consequently, the domain shapes are different, the N-terminal domain being wedge-shaped and the C-terminal domain flat. Docking studies suggest that differences in domain shape enable the N-terminal, but not C-terminal, domain of antistasin to bind and inhibit factor Xa, even though both have a very similar reactive site. Furthermore, a putative exosite binding region could be defined in the N-terminal domain of antistasin, comprising residues 15-17, which is likely to interact with a cluster of positively charged residues on the factor Xa surface (Arg222/Lys223/Lys224). This exosite binding region explains the specificity and inhibitory potency of antistasin towards factor Xa. In the C-terminal domain of antistasin, these exosite interactions are prevented due to the different overall shape of this domain. PubMed: 9311976DOI: 10.1093/emboj/16.17.5151 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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