› 5qcm

X-ray diffraction
2.2Å resolution

FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl ~{N}-[4-[[(1~{S})-2-[(~{E})-3-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]prop-2-enoyl]-3,4-dihydro-1~{H}-isoquinolin-1-yl]carbonylamino]phenyl]carbamate

Released:
DOI: 10.2210/pdb5qcm/pdb
PDB entry 5qcm coloured by chain, front view.
PDB entry 5qcm coloured by chain, side view.
PDB entry 5qcm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212).
Pinto DJP, Orwat MJ, Smith LM, Quan ML, Lam PYS, Rossi KA, Apedo A, Bozarth JM, Wu Y, Zheng JJ, Xin B, Toussaint N, Stetsko P, Gudmundsson O, Maxwell B, Crain EJ, Wong PC, Lou Z, Harper TW, Chacko SA, Myers JE, Sheriff S, Zhang H, Hou X, Mathur A, Seiffert DA, Wexler RR, Luettgen JM, Ewing WR
J Med Chem 60 9703-9723 (2017)
PMID: 29077405

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 BVJ 1 x BVJ
Ligand SO4 1 x SO4
Ligand EDO 15 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P3221
Unit cell:
a: 79.1Å b: 79.1Å c: 106.3Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.217 0.215 0.244
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

4 review citations

Plasma contact factors as therapeutic targets.
Tillman et al. (2018)
3 more