Structures of human acetylcholinesterase in complex with pharmacologically important ligands

J Med Chem. 2012 Nov 26;55(22):10282-6. doi: 10.1021/jm300871x. Epub 2012 Nov 12.

Abstract

Human acetylcholinesterase (AChE) is a significant target for therapeutic drugs. Here we present high resolution crystal structures of human AChE, alone and in complexes with drug ligands; donepezil, an Alzheimer's disease drug, binds differently to human AChE than it does to Torpedo AChE. These crystals of human AChE provide a more accurate platform for further drug development than previously available.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / metabolism
  • Acetylthiocholine / metabolism
  • Animals
  • Cholinesterase Inhibitors / metabolism*
  • Crystallography, X-Ray
  • Donepezil
  • Humans
  • Indans / metabolism*
  • Models, Molecular
  • Piperidines / metabolism*
  • Protein Conformation
  • Torpedo / metabolism*

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Acetylthiocholine
  • Donepezil
  • Acetylcholinesterase