› 6h12

X-ray diffraction
2.2Å resolution

Crystal structure of TcACHE complexed to 1-(6-Oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(4-(((1-(2-((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)pyridin-2-yl)urea

Released:
DOI: 10.2210/pdb6h12/pdb
PDB entry 6h12 coloured by chain, front view.
PDB entry 6h12 coloured by chain, side view.
PDB entry 6h12 coloured by chain, top view.
Source organism: Tetronarce californica
Primary publication:
Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3.
Oukoloff K, Coquelle N, Bartolini M, Naldi M, Le Guevel R, Bach S, Josselin B, Ruchaud S, Catto M, Pisani L, Denora N, Iacobazzi RM, Silman I, Sussman JL, Buron F, Colletier JP, Jean L, Routier S, Renard PY
Eur J Med Chem 168 58-77 (2019)
PMID: 30798053

Function and Biology Details

Reaction catalysed: 
Acetylcholine + H(2)O = choline + acetate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-137375 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Acetylcholinesterase Chains: A, B
Molecule details ›
Chains: A, B
Length: 565 amino acids
Theoretical weight: 63.76 KDa
Source organism: Tetronarce californica
UniProt:
  • Canonical: P04058 (Residues: 22-586; Coverage: 100%)
Gene name: ache
Sequence domains: Carboxylesterase family
Structure domains: alpha/beta hydrolase

Ligands and Environments

9 bound ligands:
Ligand MES 4 x MES
Ligand GOL 3 x GOL
Ligand PGE 2 x PGE
Ligand EDO 13 x EDO
Ligand SO4 3 x SO4
Ligand PEG 8 x PEG
Ligand NAG 5 x NAG
Ligand CL 6 x CL
Ligand FJK 2 x FJK
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: P212121
Unit cell:
a: 91.27Å b: 105.09Å c: 149.69Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.172 0.171 0.212

Quick links

Citations

3 review citations

Multitarget Therapeutic Strategies for Alzheimer's Disease: Review on Emerging Target Combinations.
Maramai et al. (2020)
2 more

4 mentions without citation

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches.
Cruz-Vicente et al. (2021)
3 more