The Crystallization of Acetylcholinesterase (AChE) from Torpedo Electric Organ

Abstract

The objective of this project is the crystallization of the enzyme acetylcholinesterase (AChE), with the long-term objective of determining its three-dimensional structure and, thereby, the detailed topography of its active site. Torpedo electric organ was selected since it is a rich source of AChE and possesses an amino acid sequence very similar to that of mammalian AChE. A dimeric form of this enzyme was purified by a procedure which involved selective solubilization with a phosphatidyl-inositol-specific phospholipase C of bacterial origin, followed by affinity chromatography employing a Sepharose conjugate of a suitable quaternary affinity ligand. A highly purified AChE preparation was obtained in amounts which permitted a systematic attempt to crystallize the enzyme. We were able to obtain two different crystal forms which diffract to better than 3 resolution. One of these forms, which was obtained from ammonium sulfate-phosphate buffer, is capable of being 'shock-cooled' to liquid nitrogen temperatures, which permitted X-ray data to be collected at this temperature. This 'shock-cooling' procedure prolongs the lifetime of the crystal in the X-ray beam almost indefinitely and has already permitted us to collect a preliminary set of three-dimensional X-ray data. We are thus in a position to proceed with the determination of the three-dimensional structure of AChE.

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Document Details

Document Type
Technical Report
Publication Date
Jan 25, 1988
Accession Number
ADA203411

Entities

People

  • I. Silman
  • J. L. Sussman

Organizations

  • Weizmann Institute of Science

Tags

Communities of Interest

  • Weapons Technologies

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Amino Acids
  • Animal Structures
  • Chemistry
  • Chromatography
  • Classification
  • Crystallization
  • Crystals
  • Diffraction
  • High Resolution
  • Liquid Chromatography
  • Macromolecules
  • Molecules
  • Security
  • Three Dimensional
  • X Rays
  • X-Ray Diffraction

Fields of Study

  • Chemistry

Readers

  • Molecular and Cellular Biochemistry
  • Neurotoxicology