Substrates
Under construction! AChE substrate Solution of the three-dimensional (3D) structure of Torpedo californica acetylcholinesterase (TcAChE) in 1991 [1] opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a deep and narrow gorge, lined by 14 aromatic residues (colored dark magenta), led to a revision of the views then held concerning substrate traffic, recognition and hydrolysis [2]. This led to a series of theoretical and experimental studies, which took advantage of recent advances in theoretical techniques for treatment of proteins, such as molecular dynamics and electrostatics and to site-directed mutagenesis, utilizing suitable expression systems. Acetylcholinesterase hydrolysizes the neurotransmitter acetylcholine (ACh), producing choline and an acetate group. ACh directly binds Ser200 (via its nucleophilic Oγ atom) within the catalytic triad (Ser200, His440, and Glu327) (ACh/TcAChE structure 2ace). The residues Trp84 and Phe330 are also important in the ligand recognition [3]. After this binding acetylcholinesterase hydrolysizes ACh. The Iron atom of CYP450 enzyme heme is a vital center for oxidation of substrates (drugs or other xenobiotics) Dihydrofolate reductase and its substrate dihydrofolate In a substrate reduction therapy a small molecule inhibitor (Zavesca™) is used to inhibit the synthesis of the accumulated glucosylceramide. NADH quinone oxidoreductase (NQO1) substrates Quinones (including duroquinone (2,3,5,6-tetramethyl-p-benzoquinone) are substrates of NQO1 (it catalyzes two-electron reduction of them to hydroquinones). Duroquinone (yellow) binds to the active site by interactions involving the FAD and several hydrophobic and hydrophilic residues in the duroquinone-NQO1 complex (1dxo).
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