Torpedo califomica

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. 

M. Noda, H. Takahashi, T. Tanabe, M. Toyosato, Y. Enrutani, T. Hirose, M. Asak, S. Inayama, T. Miyata, S. Numa (1982). Primary structure of a-subunit precursor of Torpedo califomica acetylchohne receptor from cDNA sequence. Nature 299 793-802. 

The detailed mechanism by which AChE and BChE hydrolyze ACh has been the subject of much research, especially since the crystal structure of the Torpedo califomica AChE was elucidated by Sussman et al. in 1991 [12]. (Reviews of these enzymes and their interactions can be found in Refs. [5,13]). This mechanism will be described here only briefly, as an introduction to the reaction of the enzyme with carbamates. The active site of AChE is located at the bottom of a 20 A-deep gorge, where acetylcholine fits in by attachment of the quaternary ammonium group to the so-called anionic site (mainly through cation interaction with the n electrons of Trp84), and by dipole interactions between the ester group and Ser200 at the esteratic site . 

Schumacher, M., Camp, S., Maulet, Y., Newton, M., MacPhee-Quigley, K., Taylor, S.S., Friedmann, T., Taylor, P. (1986). Primary structure of Torpedo califomica acetylcholinesterase deduced fi om its cDNA sequence. Nature 319 407-9. 

The determination of the three-dimensional structure of AChE from Torpedo califomica (Sussman et al, 1991) opened the way to rational redesign of cholinesterases. The possibility of converting a ChE into an OP hydrolase (OPH)... 

Noda M, Takahashi H, Tanabe T, Toyosato M, Eurutani Y, Hirose T, Asai M, Inayama S, Miyata T, Numa S. Primary structure of alpha-subunit precursor of Torpedo califomica acetylchoUne receptor deduced from cDNA sequence. Nature 1982 299 793-797. 

Observed pKj, Torpedo califomica. Predicted pKj using the GRID water probe. 

Ant venoms from the genus Solenopsis have provided an array of 2,6-disubstituted piperidines, including 197-206. A review of the fungicidal, insecticidal and repellent activity of these alkaloids has appeared [476]. Both solenopsin A (198a) and isosolenopsin A (200) were potent inhibitors (Ki = 0.16 pM and 0.24 pM, respectively) of [ HJ-perhydrohistrionicotoxin binding to sites associated with the nicotinic receptor-gated ion channel in the Torpedo califomica electric organ [477]. 

Bartolucci, C., Perola, E., Pilger, C., Pels, G. and Lamba, D. (2001) Three-dimensional structure of a complex of galanthamihe (nivalin) with acetylcholinesterase from Torpedo califomica implications for the design of new anti-Alzheimer drugs. Proteins. Struct. Fund Genet. 42 182-191. 

Huganir, R., and Racket, E. (1982). Properties of Proteoliposomes Reconstituted with Acetylcholine Receptor from Torpedo califomica," J. Biol. Chem. 257 9372-9378. 

Epstein, M., and Racker, E. (1978). Reconstitution of Carbamylcholine-dependent Sodium Ion Flux and Desensitization of the Acetylcholine Receptor from Torpedo Califomica, J. Biol. Chem. 253 6660-6662. 

The mRNA that codes for the a-subunit (obtained from Torpedo califomica) was made to generate its complementary DNA, and this was cloned. In this way, the mRNA could be prepared in quantity, and the sequence of the nucleotides mapped. This operation spelled out the order and nature of the amino acids in the a-subunit. 

The richest source of nicotinic acetylcholine receptors are the electric organs of the South American electric eel (Electrophorus electricus), the African electric catfish Malapterurus electricus) and the electric ray e.g. the marbled electric ray of the eastern Atlantic Ocean (Torpedo marmoratd) and the Californian electric ray in the northeastern Pacific (Torpedo califomica)) (Fig. 8.36). 

Occupaney of the nicotinic receptor (by A.) triggers a rapid response (1-2 ms) by direct activation of cation-selective ion channels, thereby causing depolarization of the postsynaptic membrane. The nicotinic cholinergic receptor has been isolated from the electroplax of Torpedo califomica (electric ray) and Electrophorus electricus (electric eel) and from vertebrate muscle. From all three tissues, it is a single membrane protein, M, 250,000, consisting of 4 glycoprotein subunits M, 40,000 (50,116) (a), 50,000... 

Millard, C. B., G. Koellner, A. Ordentlich, A. Shafferman, 1. Silman andj. L. Sussman,/. Am. Chem. Soc., 121,1999, 9883-9884. (Crystal structures of products of reaction of VX with Torpedo califomica AChE)... 

Sripadi, P. Nazarian, J. Hathout, Y. Hoffman, E.P. Vertes, A. In Vitro Analysis of Metabolites from the Untreated Tissue of Torpedo Califomica Electric Organ by Mid-Infrared Laser Ablation Electrospray Ionization Mass Spectrometry. Metaholomics 2009, 5, 263-276. 

Doom, J.A., Thompson, C.M., Christner, R.B., et ah, 2003. Stereoselective interaction of Torpedo califomica acetylcholinesterase by isomalathion inhibitory reactions with (IR)- and (IS)-isomers proceed by different mechanisms. Chem. Res. Toxicol. 16, 958-965. 

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