Acetylcholinesterase (Torpedo californica) (TcAChE) (TcAChE)

Acetylcholinesterase (AChE) from the Pacific electric ray, Torpedo californica, is a highly efficient serine hydrolase that plays a critical role in the termination of cholinergic neurotransmission by rapidly hydrolyzing the neurotransmitter acetylcholine into choline and acetate (UniProt P04058). Due to its high concentration in the electric organ and its ease of purification, TcAChE served as the first cholinesterase to have its three-dimensional structure determined by X-ray crystallography, making it the definitive structural model for understanding human AChE (Sussman et al., 1991, Science). The enzyme features a deep active-site gorge lined with aromatic residues, which facilitates the rapid guidance of acetylcholine to the catalytic triad consisting of Ser200, His440, and Glu327. In clinical contexts, AChE is the primary target for drugs treating Alzheimer's disease, such as Donepezil and Galantamine, which aim to compensate for cholinergic deficits (PubChem). It is also the target of various toxins, including organophosphate nerve agents and insecticides, which irreversibly inhibit the enzyme, leading to a lethal accumulation of acetylcholine (NIH/StatPearls). Consequently, TcAChE remains a cornerstone in pharmacological research for developing antidotes and more selective inhibitors, as its structural data has been instrumental in the rational design of many current therapeutic agents (Kryger et al., 1999, Structure).

Other names

AChEAcetylcholine acetylhydrolaseTcAChECholinesterase

Inhibition of the enzyme's catalytic activity, preventing the breakdown of acetylcholine and thereby increasing its concentration and duration of action at the synapse (NIH/StatPearls).