› 4x6m

X-ray diffraction
2.4Å resolution

FACTOR XIA IN COMPLEX WITH THE INHIBITOR 1-{(1S)-1-[4-(3-amino-1H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-3-[2-(aminomethyl)-5-chlorobenzyl]urea

Released:
DOI: 10.2210/pdb4x6m/pdb
PDB entry 4x6m coloured by chain, front view.
PDB entry 4x6m coloured by chain, side view.
PDB entry 4x6m coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.
Pinto DJ, Smallheer JM, Corte JR, Austin EJ, Wang C, Fang T, Smith LM, Rossi KA, Rendina AR, Bozarth JM, Zhang G, Wei A, Ramamurthy V, Sheriff S, Myers JE, Morin PE, Luettgen JM, Seiffert DA, Quan ML, Wexler RR
Bioorg Med Chem Lett 25 1635-42 (2015)
PMID: 25728130

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
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 3Y3 1 x 3Y3
Ligand SO4 1 x SO4
Ligand EDO 9 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P3221
Unit cell:
a: 78.9Å b: 78.9Å c: 106.4Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.194 0.191 0.23
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Harnessing the cyclization strategy for new drug discovery.
Tang et al. (2022)
1 more

1 mention without citation

Kinetic barriers in the isomerization of substituted ureas: implications for computer-aided drug design.
Loeffler et al. (2016)