1WSS: Human Factor Viia-tissue Factor In Complex With Peptide-mimetic Inhibitor That Has Two Charged Groups In P2 And P4

Citation:
Abstract
The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.
PDB ID: 1WSSDownload
MMDB ID: 35861
PDB Deposition Date: 2004/11/10
Updated in MMDB: 2005/12
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 1WSS: trimeric; determined by author and by software (PISA)
Molecular Components in 1WSS
Label Count Molecule
Proteins (3 molecules)
1
Coagulation Factor VII(Gene symbol: F7)
Molecule annotation
1
Coagulation Factor VII(Gene symbol: F7)
Molecule annotation
1
Tissue Factor(Gene symbol: F3)
Molecule annotation
Chemicals (12 molecules)
1
1
2
1
3
9
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.