Abstract
The possible involvement of cation-π interactions in stabilization of partially charged transition states has been investigated through examination of the kinetics of deal-kylation (‘aging’) for twelve alkyl methylphosphonyl conjugates of human acetylcholinesterase (HuAChE). These enzyme conjugates differ in the branching of the methylphosphono alkyl substituent and in the nature of the residue at position 86 of the enzyme. For conjugates of the wild type enzyme, a gradual decrease in the rates of aging, spanning two orders of magnitude, was observed for 1, 2, 2-trimethylpropyl; 1, 2-dimethylpropyl; 2-butyl and 2-propyl methylphosphonyl moieties respectively. Substitution W86→F results in a moderate decrease in the rates of aging, irrespective of the nature of the phosphonyl moiety, suggesting a similar role of the aromatic residues in the aging process. The variation of aging rates due to branching of the alkyl substituent, for the W86A conjugates was within factor ten and resembled those of limiting solvolysis reactions. These findings demonstrate that the aromatic character of the residue at position 86 is an essential element of the enzymatic environment in facilitating the aging process, and that the extent of such involvement depends upon the branching of the alkyl methylphosphonyl moiety. The generality of the biocatalytic process including cation-π stabilization of carbocationic transition state, observed in aging of phosphylated AChEs, has recently gained support from other enzymatic systems.
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© 1998 Springer Science+Business Media New York
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Barak, D. et al. (1998). The Aromatic Moiety at Position-86 of HuAChE Accelerate the Aging of Phosphonyl-AChE Conjugates through Cation-π Interactions. In: Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. (eds) Structure and Function of Cholinesterases and Related Proteins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1540-5_72
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DOI: https://doi.org/10.1007/978-1-4899-1540-5_72
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