› 1z6e

X-ray diffraction
1.8Å resolution

Factor XA in complex with the inhibitor 1-(3'-amino-1,2-benzisoxazol-5'-yl)-n-(4-(2'-((dimethylamino)methyl)-1h-imidazol-1-yl)-2-fluorophenyl)-3-(trifluoromethyl)-1h-pyrazole-5-carboxamide (razaxaban; DPC906; BMS-561389)

Released:
DOI: 10.2210/pdb1z6e/pdb
PDB entry 1z6e coloured by chain, front view.
PDB entry 1z6e coloured by chain, side view.
PDB entry 1z6e coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor.
Quan ML, Lam PY, Han Q, Pinto DJ, He MY, Li R, Ellis CD, Clark CG, Teleha CA, Sun JH, Alexander RS, Bai S, Luettgen JM, Knabb RM, Wong PC, Wexler RR
J Med Chem 48 1729-44 (2005)
PMID: 15771420

Function and Biology Details

Reaction catalysed: 
Selective cleavage of Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:
Structure domain:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133209 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Activated factor Xa heavy chain Chain: A
Molecule details ›
Chain: A
Length: 234 amino acids
Theoretical weight: 26.45 KDa
Source organism: Homo sapiens
UniProt:
  • Canonical: P00742 (Residues: 235-468; Coverage: 51%)
Gene name: F10
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases
Factor X light chain Chain: L
Molecule details ›
Chain: L
Length: 52 amino acids
Theoretical weight: 5.59 KDa
Source organism: Homo sapiens
UniProt:
  • Canonical: P00742 (Residues: 127-178; Coverage: 11%)
Gene name: F10
Sequence domains: Coagulation Factor Xa inhibitory site
Structure domains: Laminin

Ligands and Environments

1 bound ligand:
Ligand IK8 1 x IK8
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 5ID-B
Spacegroup: P212121
Unit cell:
a: 56.1Å b: 71.7Å c: 78.3Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.221 0.219 0.26

Quick links

Citations

9 review citations

Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor.
Wong et al. (2011)
8 more

5 mentions without citation

Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.
Abel et al. (2008)
4 more