Sandbox 12345
From Proteopedia
Acetylcholinesterase in complex with tacrine
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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.
