Open AccessStructure‐Activity Relationships in Acetylcholinesterase Reactions
Author(s) -
JÄRV Jaak,
KESVATERA Tônu,
AAVIKSAAR Aavo
Publication year - 1976
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1976.tb10694.x
Subject(s) - chemistry , acetylcholinesterase , steric effects , michaelis–menten kinetics , enzyme kinetics , ionic strength , substrate (aquarium) , leaving group , reaction rate constant , acetylation , stereochemistry , hydrolysis , active site , stereospecificity , medicinal chemistry , kinetics , enzyme , organic chemistry , catalysis , enzyme assay , aqueous solution , biochemistry , oceanography , physics , quantum mechanics , gene , geology
The Michaelis‐Menten parameters k cat K s(app) and the second‐order rate constants k 11 = k 2 /K s of acetylcholinesterase‐catalyzed hydrolysis of 25 acetic esters with note‐ionic leaving groups have been determined at 25 °C and pH 7.5 in 0.15 M KCL A linear relationship between the substrate non‐covalent binding capacity and the leaving group hydrophobicity, and a multiparameter correlation of the acetylation reaction rate constant logarithm with the leaving group, inductive effect, hydrophobicity, and steric effect, have been established. The acetyl‐enzyme deacetylation rate constant has been calculated. Taken together, a fairly complete understanding of acetylcholinesterase specificity is possible. The data are consistent with a model of the acetylcholinesterase active site, in which the catalytically active groups are located at the bottom of a jaws‐like slit with a limited range of hydrophobic walls that provide the sorption of the substrate leaving groups not longer than that in n‐butyl acetate.