› 6rav

X-ray diffraction
1.7Å resolution

Complement factor B protease domain in complex with the reversible inhibitor 4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid

Released:
DOI: 10.2210/pdb6rav/pdb
PDB entry 6rav coloured by chain, front view.
PDB entry 6rav coloured by chain, side view.
PDB entry 6rav coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Small-molecule factor B inhibitor for the treatment of complement-mediated diseases.
Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM, Mac Sweeney A, Liao SM, Crowley M, Littlewood-Evans A, Sarret S, Wieczorek G, Perrot L, Dubost V, Flandre T, Zhang Y, Smith RJH, Risitano AM, Karki RG, Zhang C, Valeur E, Sirockin F, Gerhartz B, Erbel P, Hughes N, Smith TM, Cumin F, Argikar UA, Haraldsson B, Mogi M, Sedrani R, Wiesmann C, Jaffee B, Maibaum J, Flohr S, Harrison R, Eder J
Proc Natl Acad Sci U S A 116 7926-7931 (2019)
PMID: 30926668

Function and Biology Details

Reaction catalysed: 
Cleavage of Arg-|-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-|- bond in complement component C5 alpha-chain to yield C5a and C5b.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133303 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Complement factor B Bb fragment Chains: AAA, BBB
Molecule details ›
Chains: AAA, BBB
Length: 291 amino acids
Theoretical weight: 32.96 KDa
Source organism: Homo sapiens
Expression system: Drosophila melanogaster
UniProt:
  • Canonical: P00751 (Residues: 474-764; Coverage: 39%)
Gene names: BF, BFD, CFB
Sequence domains: Trypsin

Ligands and Environments

3 bound ligands:
Ligand SO4 5 x SO4
Ligand JGQ 2 x JGQ
Ligand ZN 2 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 54.463Å b: 97.446Å c: 61.815Å
α: 90° β: 100.475° γ: 90°
R-values:
R R work R free
0.197 0.195 0.227
Expression system: Drosophila melanogaster

Quick links

Citations

33 review citations

Clinical promise of next-generation complement therapeutics.
Mastellos et al. (2019)
32 more

1 mention without citation

Low-molecular weight inhibitors of the alternative complement pathway.
Schubart et al. (2023)