Brain fasciculins

Fasciculins inhibit AChE from mammals, electric fish, and some snake venoms with Ki values in the pico- to nanomolar range in contrast, avian, insect, and some other snake venom AChEs are relatively resistant, and high micromolar concentrations are required to inhibit mammalian butyrylcholinesterases (BuChE) (Marchot et al, 1993). Dissociation constants of Fasl and Fas3 are two-fold and 60-fold lower, respectively, than that of Fas2 for synaptosomal rat brain. 

Binding of I-fasciculin to rat brain acetylcholinesterase. The complex still binds diisopropyl fluorophosphate. J. Biol. Chem. 268 12458-67. 

Marchot, P, Khclif. A, Ji, Y. H., Mansuclle. P., and Bougis, P. H. (1993). Binding of 1251-fasciculin to rat brain acctyl-choline.slerase. The complex. still binds dii.sopropyl tluo-rophosphate. J. Biol. Chem. 268, 12458-12467. 

A large number of organic compounds reversible or irreversibly inhibits AChE (Long, 1963), which bind either to the esteratic or the anionic subsite of AChE catalytic site or to the peripheral site of the enzymes. Most of them are S5mthetic substances, sometimes with insecticidal properties. Few natural inhibitors of AChE are known and, to date, fasciculins are the only known proteinic AChE inhibitors. They have been shown to display a powerful inhibitory activity toward mammalian AChE. lodination of Fas3 provided a fully active and specific probe of fasciculin-binding sites on rat brain AChE (Marchot et al., 1993). These authors demonstrate that fasciculins bind on a peripheral site of AChE, distinct from the catalytic site and, at least partly, common with the sites on which some cationic inhibitors and the substrate in excess bind since phosphorylation of the catalytic serine (esteratic subsite) by [l,3- H]diisopro-pyl fluorophosphate can still occur on the Fas3. In the... 

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