PDBsum entry 1skz

Serine protease inhibitor

PDB id: 1skz

Contents

Protein chain

104 a.a.

Metals

_CL

Waters ×88

PDB id:

1skz

Name:

Serine protease inhibitor

Title:

Protease inhibitor

Structure:

Antistasin. Chain: a. Synonym: factor xa inhibitor. Engineered: yes. Mutation: yes

Source:

Haementeria officinalis. Mexican leech. Organism_taxid: 6410. Organ: blood. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.217

Authors:

U.Krengel,B.W.Dijkstra

Key ref:

R.Lapatto et al. (1997). X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa. Embo J, 16, 5151-5161. PubMed id: 9311976 DOI: 10.1093/emboj/16.17.5151

Date:

16-Apr-97 Release date: 22-Oct-97

Protein chain

P15358  (ANTA_HAEOF) -  Antistasin from Haementeria officinalis

Seq: 136 a.a.

Struc: 104 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1093/emboj/16.17.5151

Embo J 16:5151-5161 (1997)

PubMed id: 9311976

X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa.

R.Lapatto, U.Krengel, H.A.Schreuder, A.Arkema, B.de Boer, K.H.Kalk, W.G.Hol, P.D.Grootenhuis, J.W.Mulders, R.Dijkema, H.J.Theunissen, B.W.Dijkstra.

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.

Selected figure(s)

Figure 4.
Figure 4 Stereo view showing the superposition of the N- and C-terminal domains of antistasin, based on the C coordinates of the second subdomains, respectively [using the program O (Jones et al., 1991); figure produced with Molscript (Kraulis, 1991)]. The N-terminal domain (black) adopts a wedge shape, while the C-terminal domain (grey) is relatively flat.

Figure 5.
Figure 5 Schematic representation of the antistasin fold. The orientation of antistasin is similar to the one chosen in Figure 3. Disulfide connectivities and the linker residues connecting the two subdomains within each domain are indicated. The scissile bond is marked by an arrow. -strands involve amino acid residues 41 -43 and 49 -53 in the N-terminal domain and residues 96 -98 and 104 -108 in the C-terminal domain, respectively.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Embo J (1997, 16, 5151-5161) copyright 1997.

Figures were selected by an automated process.