› 8dea

X-ray diffraction
2.21Å resolution

Scaffold Hopping via Ring Opening Enables Identification of Acyclic Compounds as New Complement Factor D Inhibitors

Released:
DOI: 10.2210/pdb8dea/pdb
PDB entry 8dea coloured by chain, front view.
PDB entry 8dea coloured by chain, side view.
PDB entry 8dea coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Scaffold hopping via ring opening enables identification of acyclic compounds as new complement Factor D inhibitors.
Zhang W, Wu M, Vadlakonda S, Juarez L, Cheng X, Muppa S, Chintareddy V, Vogeti L, Kellogg-Yelder D, Williams J, Polach K, Chen X, Raman K, Babu YS, Kotian P
Bioorg Med Chem 74 117034 (2022)
PMID: 36272185

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 Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 230 amino acids
Theoretical weight: 24.6 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P00746 (Residues: 26-253; Coverage: 98%)
Gene names: CFD, DF, PFD
Sequence domains: Trypsin

Ligands and Environments

2 bound ligands:
Ligand R7X 4 x R7X
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007
Unit cell:
a: 44.898Å b: 73.032Å c: 240.864Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.229 0.225 0.3
Expression system: Homo sapiens

Quick links

Citations

1 review citation

Complement in human disease: approved and up-and-coming therapeutics.
West et al. (2024)