Acetylcholinesterase acyl pocket

The cholinesterases, acetylcholinesterase and butyrylcholinesterase, are serine hydrolase enzymes. The biological role of acetylcholinesterase (AChE, EC 3.1.1.7) is to hydrolyze the neurotransmitter acetylcholine (ACh) to acetate and choline (Scheme 6.1). This plays a role in impulse termination of transmissions at cholinergic synapses within the nervous system (Fig. 6.7) [12,13]. Butyrylcholinesterase (BChE, EC 3.1.1.8), on the other hand, has yet not been ascribed a function. It tolerates a large variety of esters and is more active with butyryl and propio-nyl choline than with acetyl choline [14]. Structure-activity relationship studies have shown that different steric restrictions in the acyl pockets of AChE and BChE cause the difference in their specificity with respect to the acyl moiety of the substrate [15]. AChE hydrolyzes ACh at a very high rate. The maximal rate for hydrolysis of ACh and its thio analog acetyl-thiocholine are around 10 M s , approaching the diffusion-controlled limit [16]. 

In contrast to acetylcholinesterase, which is selective for acetylcholine, butyryl-cholinesterase tolerates a wider variety of esters and is more active with butyryl-and propionylcholines than acetylcholine [7]. Structure-activity relationship studies have shown that different steric restrictions in the acyl pockets of AChE and BChE cause the difference in specificity to the acyl moiety of the substrate [6]. 

Ordentlich, A., Barak, D., Kronman, C, Flashner, V, Leitncr. M., Segall, Y., Ariel, N., Cohen. S Velan, B, and Shafferman, A, (1993). Dis.seciion of the human acetylcholinesterase active center deteiminant.s of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket. J. Biol. Chem. 268, 17083-17095. 

---