Acetylcholine binding site model

A 3D model of the receptor binding site has been worked out with the aid of conformationally restrained analogues of acetylcholine. Acetylcholine itself has no conformational restraints. It is a straight-chain molecule in which bond rotation along the length of its chain can lead to numerous possible conformations (or shapes). Thus, it is impossible to know exactly the 3D shape of the receptor site from considering acetylcholine alone. In the past, it was assumed that a flexible neurotransmitter such as acetylcholine would interact with its receptor in its most stable conformation. In the case of acetylcholine, that would be the conformation represented by the sawhorse and Newman projections shown in Fig. 11.12. 

Figure 5. Model of the proposed acetylcholine recognition site on the alpha subunit of the Torpedo ACh receptor in the region between Cys 128 and Cys 142. An ACh molecule is shown in relation to the four residues postulated to interact in its binding. Reprinted with permission from Ref. 9. Copyright 1985 Elsevier Science Publishers.

The most important part of the enzyme is its active site, where the acetylcholine and the many inhibitors bind. The classical model shown in Figure 5.3 (Nachmansohn and Wilson, 1951) is still very useful, although not exactly correct. The model says that acetylcholinesterase has two subsites in the active site called the esteratic and anionic sites. Because acetylcholine is an ester where the alcoholic part (choline) carries a positive charge, this part... 

A model of cholinesterase has been proposed that is consistent with all of the information available (Fig. 35). In the model there are two sites of attachment, an anionic site that binds the cationic quarternary nitrogen group and an esteratic site that reacts with the carbon of the carbonyl moiety of the ester. When acetylcholine is adsorbed to the enzyme, a transfer of the carbonyl group to the enzyme takes place, forming... 

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