› 6h14

X-ray diffraction
1.86Å 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)pyridin-2-yl)urea

Released:
DOI: 10.2210/pdb6h14/pdb
PDB entry 6h14 coloured by chain, front view.
PDB entry 6h14 coloured by chain, side view.
PDB entry 6h14 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
Macromolecules (2 distinct):
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

Carbohydrate polymer : NEW Components: NAG
Carbohydrate polymer
9 bound ligands:
Ligand NAG 5 x NAG
Ligand EDO 8 x EDO
Ligand PEG 1 x PEG
Ligand GOL 2 x GOL
Ligand FW8 2 x FW8
Ligand PGE 2 x PGE
Ligand SO4 1 x SO4
Ligand CL 1 x CL
Ligand MES 1 x MES
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE MASSIF-1
Spacegroup: P212121
Unit cell:
a: 91.591Å b: 107.926Å c: 150.698Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.178 0.177 0.211

Quick links

Citations

3 review citations

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

2 mentions without citation

Germline IgM predicts T cell immunity to Pneumocystis.
Noell et al. (2022)
1 more