› 4y8z

X-ray diffraction
2.2Å resolution

Factor XIa in complex with the inhibitor (2E)-N-[(1S)-1-[5-chloro-4-(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yl)-1H-imidazol-2-yl]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enamide

Released:
DOI: 10.2210/pdb4y8z/pdb
PDB entry 4y8z coloured by chain, front view.
PDB entry 4y8z coloured by chain, side view.
PDB entry 4y8z coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a Potent Parenterally Administered Factor XIa Inhibitor with Hydroxyquinolin-2(1H)-one as the P2' Moiety.
Hu Z, Wong PC, Gilligan PJ, Han W, Pabbisetty KB, Bozarth JM, Crain EJ, Harper T, Luettgen JM, Myers JE, Ramamurthy V, Rossi KA, Sheriff S, Watson CA, Wei A, Zheng JJ, Seiffert DA, Wexler RR, Quan ML
ACS Med Chem Lett 6 590-5 (2015)
PMID: 26005539

Function and Biology Details

Reaction catalysed: 
Selective cleavage of Arg-|-Ala and Arg-|-Val bonds in factor IX to form factor IXa.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-137278 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Coagulation factor XIa light chain Chain: A
Molecule details ›
Chain: A
Length: 244 amino acids
Theoretical weight: 27.6 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03951 (Residues: 388-625; Coverage: 39%)
Gene name: F11
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases

Ligands and Environments

3 bound ligands:
Ligand 4CE 1 x 4CE
Ligand SO4 1 x SO4
Ligand EDO 5 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-BM
Spacegroup: P3221
Unit cell:
a: 79.1Å b: 79.1Å c: 106.4Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.24 0.239 0.261
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

3 citation in other articles

Novel phenylalanine derived diamides as Factor XIa inhibitors.
Smith et al. (2016)
2 more

2 mentions without citation

Factor XIa inhibitors: A review of the patent literature.
Al-Horani et al. (2016)
1 more