Molecular dissection of cholinesterase domains responsible for carbamate toxicity.

摘要: Abstract Carbamate compounds marked for their cholinesterase (ChE) inhibition are widely used as therapeutics and insecticides. Groups of closely related carbamate molecules provide an important tool in the understanding domains responsible binding these ligands to ChEs. Comparative profiles were derived five N-methyl carbamates, mostly carbofuran derivatives, differing length branching hydrocarbonic chain towards human erythrocyte acetylcholinesterase (H.AChE), serum butyrylcholinesterase (H.BChE) its normal form or a mutant containing point mutation Asp70→Gly, Drosophila nervous system ChE. Carbofuran was more toxic all three ChEs than any other with IC50 values which differed by 1000-fold. ChE appeared be most sensitive examined H. AChE consistently BChE. Morever, efficiency BChE decreased effectively it did increased complexity side chain, indicating less flexible site compared AChE. The Asp70→Gly had no apparent effect on suggesting that Asp70 domain localized near rim active groove is not binding. Comparison published LD50 demonstrated correlation between vivo toxicity biological addition scavenging importance mammals. Pinpointing different characteristic each member family can thus shed light variable inhibitors insects mammals, predict yet untested inhibitor help designing novel improved inhibitors.