From Proteopedia
proteopedia linkproteopedia link Acetylcholinesterase in complex with tacrine
In the crystal structure of Torpedo californica acetylcholinesterase
(TcAChE) complexed with tacrine (THA), THA's acridine ring is stacked
between the aromatic rings of , near the catalytic triad
of AChE's active site which consists of S200, E327, H440. When
comparing 3 recent complexes of TcAChE, i.e. edrophonium (EDR),
decamethonium (DECA) and THA, the only major conformational difference
between them is seen in the orientation of the phenyl ring of F330. In
the DECA complex it lies parallel to the surface of the gorge; in the
other two complexes it is positioned to make contact with the bound
ligand. This close interaction was confirmed [1] by photoaffinity labeling
by a 3H-labeled photosensitive probe, which labeled, predominantly,
F330 within the active site. Labeling of W279 was also observed. One
mole of label is incorporated per mole of AChE inactivated, indicating
that labeling of W279 and that of F330 are mutually exclusive. The
structural and chemical data, together, show the important role of
aromatic groups as binding sites for quaternary ligands, and they
provide complementary evidence assigning W84 and F330 to the "anionic"
subsite of the active site and W279 to the "peripheral" anionic site.
