title: Ligand stabilization of cholinesterases.
abstract: Stabilization of fetal bovine serum (FBS) acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) (AChE) and human butyrylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) (BuChE) by ligands and inhibitors was studied as a function of physical and chemical perturbation. Denaturation of AChE occurred as a binary exponential function in the temperature range studied (50-56 degrees C); the slower fraction progressively diminished as the temperature was increased. Inclusion of ligands or inhibitors stabilized AChE as a function of temperature, ligand concentration and time. The rank order in which ligands stabilized AChE was: edrophonium greater than decamethonium greater than pralidoxime chloride much greater than procainamide. BuChE denaturation was retarded by ligands in the order: decamethonium greater than procainamide greater than edrophonium greater than pralidoxime. A plot of the quotient of the fast/slow ratio against the log of the 50% inhibitory concentration (I50) for ligands providing substantial protection yielded a linear relation, suggesting that these compounds stabilized AChE by a common mechanism involving the anionic site of the active center. Urea-induced cholinesterase denaturation was also retarded by these ligands.
authors: Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC.
authors: C S
authors: CS
authors: Payne
authors: M
authors: M
authors: Saeed
authors: A D
authors: AD
authors: Wolfe
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002417:Cattle; D002802:Cholinesterases / Q000378:metabolism*; D003650:Decamethonium Compounds / Q000494:pharmacology; D004491:Edrophonium / Q000494:pharmacology; D004795:Enzyme Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D013696:Temperature
chemical_list: D003650:Decamethonium Compounds; D008024:Ligands; D011220:Pralidoxime Compounds; D004491:Edrophonium; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases; D011342:Procainamide; C028797:pralidoxime