Structure of acetylcholinesterase

Sussman, J.L., Harel, M., and Frolow, F. et al. (1991). Atomic structure of acetylcholinesterase from Torpedo califomica a prototypic acetylcholine-binding protein. Science 253, 872-879. 

J. L. Sussman, M. Harel, F. Frolow, C. Oefner, A. Goldman, L. Toker, I. Silman, Atomic Structure of Acetylcholinesterase from Torpedo califomica A Prototypic Acetylcholine-Binding Protein , Science 1991, 253, 872 - 879. 

Greenblatt HM, Kryger G Lewis T, Sihnan 1, Sussman JL. (1999) Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEES Lett 463 321-326. 

P. Taylor, M. Schumacher, K. MacPhee-Quigley, T. Friedman, S. Taylor (1987). The structure of acetylcholinesterase relationships to its function and cellular disposition. Trends Neurosci. 10 92-96. 

Kryger, G., Silman, I., Sussman, J.L. Structure of Acetylcholinesterase Complexed with E2020 (Aricept) Implications for the Design of New Anti-Alz-heimer Drugs. Struct. Fold. Des. 1999, 15, 297-307. 

Coordination by oxygen atoms is not the only mechanism with which cations can be bound in the cavity of a natural or non-natural receptor, however. The crystal structure of acetylcholinesterase, an enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine into choline and acetate, with the inhibitor deca-methonium (Me3N+(CH2)ioNMe3+) included inside the active center showed an... 

Detailed studies of the molecular structure of acetylcholinesterase (AChE) have shown that this enzyme exists in many molecular forms [43], There are globular (G) and asymmetric classes, which are further subdivided. The... 

Ekstrom, F. et al. Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime structural basis for differences in the ability to reactivate tabun conjugates, Biochem. Pharmacol., 72, 597, 2006a. 

Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica a prototypic acetylcholinebinding protein. Science 1991 253 872-879. 

Figure 1. Schematic of the probable physical structure of acetylcholinesterase. One physical region carries the esteratic site, which is proximal to one anionic site (Site I) the other region would carry at least four anionic sites, and would be homologous to the acetylcholine receptor of the motor end plate excitable membrane. Sites I and II are masked by DPA, but Site II can be regenerated at alkaline pH. Decamethonium (C10) would interact at least with Sites I and II whereas curare would bind at III and TV, and perhaps at II and III. Most quaternary salt substituents bind on the anionic chain [exo-binding (26, 36, 42.

Contrary to this, Hollingworth et al. (1967) traced back the toxicity-reducing effect of the 3-methyl group to a difference in the structure of acetylcholinesterase of insects and those of vertebrates. They found that the substituent on the phenyl ring in position 3 forms in the order H < methyl < isopropyl a bond of increasing strength between the enzyme from fly heads and the toxic compound, while the reverse order was found in the case of bovine erythrocyte acetylcholinesterase. From this they concluded that the distance between the anionic and esteratic centres is 0.1 nm larger in the insect enzyme than in the mammalian enzyme. 

Kryger, G., Sdman, 1., and Sussman, J.L. (1999) Structure of acetylcholinesterase complexed with E2020 (Aricept (R)) implications for the design of new anti-Alzheimer drugs. Structure, 7, 297-307. 

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