Anionic site interactions in human butyrylcholinesterase disrupted by two single point mutations

Structure-function relationships of recombinant human butyrylcholinesterase (CHE) variants were investigated by Xenopus oocyte microinjection. A Ser-425 to Pro-425 mutation failed to modify ligand binding properties. In contrast, Asp-70 to Gly-70 substitution significantly reduced CHE binding capaci...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-12, Vol.265 (34), p.20735-20738
Main Authors: Neville, L F, Gnatt, A, Padan, R, Seidman, S, Soreq, H
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Anions
Binding Sites
Biological and medical sciences
Brain Neoplasms - enzymology
Butyrylcholinesterase - genetics
Butyrylcholinesterase - metabolism
Cholinesterase Inhibitors - pharmacology
Dibucaine - pharmacology
DNA, Neoplasm - genetics
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Genetic Variation
Glioma - enzymology
Humans
Hydrolases
microinjection
Mutagenesis, Site-Directed
Neuroblastoma - enzymology
Recombinant Proteins - metabolism
Substrate Specificity
Succinylcholine - pharmacology
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Summary:Structure-function relationships of recombinant human butyrylcholinesterase (CHE) variants were investigated by Xenopus oocyte microinjection. A Ser-425 to Pro-425 mutation failed to modify ligand binding properties. In contrast, Asp-70 to Gly-70 substitution significantly reduced CHE binding capacity for succinylcholine and specific inhibitors, demonstrating Asp-70 as a key anionic site component for certain ligands. Furthermore, the presence of both mutations rendered CHE totally resistant to succinylcholine and dibucaine inhibition, while all mutant proteins bound butyrylthiocholine, benzoylcholine, and propionylcholine normally. These findings imply structural interactions between the conserved Asp-70 and Ser-425 regions in cholinesterases and suggest the contribution of additional electronegative amino acids to anionic site binding.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(17)45277-X