› 5q0e

X-ray diffraction
2.12Å resolution

FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(4S,8S)-8-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-4-methyl-2-oxo-1,3,4,5,6,7,8,10-octahydro-2H-12,9-(azeno)-1,10-benzodiazacyclotetradecin-15-yl]carbamate

Released:
DOI: 10.2210/pdb5q0e/pdb
PDB entry 5q0e coloured by chain, front view.
PDB entry 5q0e coloured by chain, side view.
PDB entry 5q0e coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Macrocyclic inhibitors of Factor XIa: Discovery of alkyl-substituted macrocyclic amide linkers with improved potency.
Corte JR, Yang W, Fang T, Wang Y, Osuna H, Lai A, Ewing WR, Rossi KA, Myers JE, Sheriff S, Lou Z, Zheng JJ, Harper TW, Bozarth JM, Wu Y, Luettgen JM, Seiffert DA, Quan ML, Wexler RR, Lam PYS
Bioorg Med Chem Lett 27 3833-3839 (2017)
PMID: 28687203

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 9FD 1 x 9FD
Ligand SO4 2 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: 78.8Å b: 78.8Å c: 106Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.174 0.173 0.196
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

2 review citations

Discovery methods of coagulation-inhibiting drugs.
Gómez-Outes et al. (2017)
1 more