2H9E: Crystal Structure Of Fxa/selectide/napc2 Ternary Complex

Citation:
Abstract
NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K(i)=8.4 pM) of the factor VIIa/tissue factor complex. NAPc2 is highly flexible, becoming partially ordered and undergoing significant structural changes in the C terminus upon binding to the factor Xa exosite. In the crystal structure of the ternary factor Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular antiparallel beta-sheet formed by the segment of the polypeptide chain consisting of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is additional maintained by contacts between the short helical segment (residues 67-73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of factor Xa (residues 233-243). This exosite is physiologically highly relevant for the recognition and inhibition of factor X/Xa by macromolecular substrates and provides a structural motif for the development of a new class of inhibitors for the treatment of deep vein thrombosis and angioplasty.
PDB ID: 2H9EDownload
MMDB ID: 44472
PDB Deposition Date: 2006/6/9
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Ancylostoma caninum
Similar Structures:
Biological Unit for 2H9E: tetrameric; determined by author and by software (PISA)
Molecular Components in 2H9E
Label Count Molecule
Proteins (4 molecules)
1
Coagulation Factor X Heavy Chain(Gene symbol: F10)
Molecule annotation
1
Coagulation Factor X Light Chain(Gene symbol: F10)
Molecule annotation
1
Anti-coagulant Protein C2
Molecule annotation
1
Selectide Inhibitor Dty-ile-arg-leu-lpd Peptide
Molecule annotation
Chemicals (10 molecules)
1
6
2
3
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.