› 3kl6

X-ray diffraction
1.45Å resolution

Discovery of Tetrahydropyrimidin-2(1H)-one derivative TAK-442: A potent, selective and orally active factor Xa inhibitor

Released:
DOI: 10.2210/pdb3kl6/pdb
PDB entry 3kl6 coloured by chain, front view.
PDB entry 3kl6 coloured by chain, side view.
PDB entry 3kl6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor.
Fujimoto T, Imaeda Y, Konishi N, Hiroe K, Kawamura M, Textor GP, Aertgeerts K, Kubo K
J Med Chem 53 3517-31 (2010)
PMID: 20355714

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 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: 241 amino acids
Theoretical weight: 27.2 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P00742 (Residues: 235-475; Coverage: 53%)
Gene name: F10
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases
Factor X light chain Chain: B
Molecule details ›
Chain: B
Length: 57 amino acids
Theoretical weight: 6.19 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P00742 (Residues: 126-179; Coverage: 12%)
Gene name: F10
Sequence domains: Coagulation Factor Xa inhibitory site
Structure domains: Laminin

Ligands and Environments

3 bound ligands:
Ligand 443 1 x 443
Ligand EDO 4 x EDO
Ligand CA 3 x CA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P212121
Unit cell:
a: 49.002Å b: 70.345Å c: 78.546Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.195 0.194 0.212
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

Oral, direct thrombin and factor Xa inhibitors: the replacement for warfarin, leeches, and pig intestines?
Straub et al. (2011)
1 more

8 mentions without citation

Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking.
Mysinger et al. (2012)
7 more