› 5nat

X-ray diffraction
1.17Å resolution

Complement factor D in complex with the inhibitor (S)-Pyrrolidine-1,2-dicarboxylic acid 1-[(1-methyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide]

Released:
DOI: 10.2210/pdb5nat/pdb
PDB entry 5nat coloured by chain, front view.
PDB entry 5nat coloured by chain, side view.
PDB entry 5nat coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition in Vivo.
Lorthiois E, Anderson K, Vulpetti A, Rogel O, Cumin F, Ostermann N, Steinbacher S, Mac Sweeney A, Delgado O, Liao SM, Randl S, Rüdisser S, Dussauge S, Fettis K, Kieffer L, de Erkenez A, Yang L, Hartwieg C, Argikar UA, La Bonte LR, Newton R, Kansara V, Flohr S, Hommel U, Jaffee B, Maibaum J
J Med Chem 60 5717-5735 (2017)
PMID: 28621538

Function and Biology Details

Reaction catalysed: 
Selective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133224 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Complement factor D Chain: A
Molecule details ›
Chain: A
Length: 232 amino acids
Theoretical weight: 24.74 KDa
Source organism: Homo sapiens
UniProt:
  • Canonical: P00746 (Residues: 26-253; Coverage: 98%)
Gene names: CFD, DF, PFD
Sequence domains: Trypsin
Structure domains: Trypsin-like serine proteases

Ligands and Environments

2 bound ligands:
Ligand GOL 2 x GOL
Ligand 8RT 1 x 8RT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 39.438Å b: 49.676Å c: 55.562Å
α: 90° β: 106.02° γ: 90°

Quick links

Citations

7 review citations

Complement System and Potential Therapeutics in Age-Related Macular Degeneration.
Park et al. (2021)
6 more

1 mention without citation

Exploring Prognostic Biomarkers of Acute Myeloid Leukemia to Determine Its Most Effective Drugs from the FDA-Approved List through Molecular Docking and Dynamic Simulation.
Alom et al. (2023)