Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein

Science. 1991 Aug 23;253(5022):872-9. doi: 10.1126/science.1678899.

Abstract

The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Membrane / enzymology
  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallization
  • Electric Organ / enzymology*
  • Glutamates
  • Glutamic Acid
  • Macromolecular Substances
  • Molecular Sequence Data
  • Molecular Structure
  • Phosphatidylinositols / metabolism
  • Protein Conformation
  • Sequence Homology, Nucleic Acid
  • Torpedo*
  • X-Ray Diffraction

Substances

  • Glutamates
  • Macromolecular Substances
  • Phosphatidylinositols
  • Glutamic Acid
  • Acetylcholinesterase
  • Acetylcholine