› 7aiy

X-ray diffraction
2.94Å resolution

Crystal structure of human butyrylcholinesterase in complex with 2-{1-[4-(12-Amino-3-chloro-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinolin-9-yl)butyl]-1H-1,2,3-triazol-4-yl}-N-[4-hydroxy-3-methoxybenzyl]acetamide

Released:
DOI: 10.2210/pdb7aiy/pdb
PDB entry 7aiy coloured by chain, front view.
PDB entry 7aiy coloured by chain, side view.
PDB entry 7aiy coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice.
Viayna E, Coquelle N, Cieslikiewicz-Bouet M, Cisternas P, Oliva CA, Sánchez-López E, Ettcheto M, Bartolini M, De Simone A, Ricchini M, Rendina M, Pons M, Firuzi O, Pérez B, Saso L, Andrisano V, Nachon F, Brazzolotto X, García ML, Camins A, Silman I, Jean L, Inestrosa NC, Colletier JP, Renard PY, Muñoz-Torrero D
J Med Chem 64 812-839 (2021)
PMID: 33356266

Function and Biology Details

Reaction catalysed: 
An acylcholine + H(2)O = choline + a carboxylate
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138983 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cholinesterase Chains: A, B
Molecule details ›
Chains: A, B
Length: 602 amino acids
Theoretical weight: 68.49 KDa
Source organism: Homo sapiens
Expression system: Cricetulus griseus
UniProt:
  • Canonical: P06276 (Residues: 1-602; Coverage: 100%)
Gene names: BCHE, CHE1
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand 8U2 1 x 8U2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE MASSIF-3
Spacegroup: P212121
Unit cell:
a: 73.878Å b: 79.318Å c: 228.71Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.229 0.225 0.3
Expression system: Cricetulus griseus

Quick links

Citations

2 review citations

Tacrine-Based Hybrids: Past, Present, and Future.
Bubley et al. (2023)
1 more

4 mentions without citation

Dual-target ligand discovery for Alzheimer's disease: triphenylphosphoranylidene derivatives as inhibitors of acetylcholinesterase and β-amyloid aggregation.
El-Hussieny et al. (2023)
3 more