Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.
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.
Department of Structural Chemistry, Weizmann Institute of Science, Rehovot, Israel.
J L
JL
Sussman
M
M
Harel
F
F
Frolow
C
C
Oefner
A
A
Goldman
L
L
Toker
I
I
Silman
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004557:Electric Organ / Q000201:enzymology*; D005971:Glutamates; D018698:Glutamic Acid; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010716:Phosphatidylinositols / Q000378:metabolism; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D014101:Torpedo; D014961:X-Ray Diffraction
D005971:Glutamates; D046911:Macromolecular Substances; D010716:Phosphatidylinositols; D018698:Glutamic Acid; D000110:Acetylcholinesterase; D000109:Acetylcholine