Biomaterial Database

Fasciculin inhibition of acetylcholinesterase is prevented by chemical modification of the enzyme at a peripheral site. 1994

R Durán, and C Cerveñansky, and F Dajas, and K F Tipton

Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.

Fasciculin 2 (FAS) is a 61 amino acid peptide present in Dendroaspis angusticeps snake venom, with a selective and potent inhibitory activity towards acetylcholinesterase (AChE). The specific interaction of FAS with peripheral sites present in Electrophorus electricus AChE (Ki = 0.04 nM FAS) was investigated by chemical modification with N,N-dimethyl-2-phenylaziridinium (DPA) in the presence of active or peripheral anionic site protective agents. An enzyme was obtained that compared to the native AChE is 10(6)-times less sensitive to FAS, is fully inhibited by edrophonium and tacrine, and is 25-170-times less sensitive to several peripheral site ligands. Characterization of catalytic functions showed that Km for acetylthiocholine was 4-fold lower in the DPA-modified enzyme, whereas Km for phenylacetate remained the same. Values for Kcat determined with both substrates were unchanged. Diminished catalytic efficiency reflects that hydrolysis and/or supply of cationic substrates to the active site was affected by DPA reaction at a peripheral site. Previous data implicate Trp-279 (Torpedo AChE sequence numbering) as the residue actually involved in DPA modification. Our results strongly support FAS binding to an AChE peripheral site which partially overlaps the site of other peripheral site ligands including acetylthiocholine.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004546	Elapid Venoms	Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.	Cobra Venoms,Elapidae Venom,Elapidae Venoms,Naja Venoms,Cobra Venom,Elapid Venom,Hydrophid Venom,Hydrophid Venoms,King Cobra Venom,Naja Venom,Ophiophagus hannah Venom,Sea Snake Venom,Sea Snake Venoms,Venom, Cobra,Venom, Elapid,Venom, Elapidae,Venom, Hydrophid,Venom, King Cobra,Venom, Naja,Venom, Ophiophagus hannah,Venom, Sea Snake,Venoms, Cobra,Venoms, Elapid,Venoms, Elapidae,Venoms, Hydrophid,Venoms, Naja,Venoms, Sea Snake
D004593	Electrophorus	A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.	Eel, Electric,Electric Eel,Electrophorus electricus
D000110	Acetylcholinesterase	An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.	Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001388	Aziridines	Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms.	Ethyleneimines,Azacyclopropanes, Saturated,Dimethyleneimines,Saturated Azacyclopropanes
D014101	Torpedo	A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.	Electric Rays,Torpedinidae,Rays, Electric