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

L F Neville, A Gnatt, S Seidman, H Soreq, Ruth Ashery Padan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)20735-8
Number of pages4
JournalThe Journal of biological chemistry
Issue number34
StatePublished - 5 Dec 1990


  • Anions
  • Binding Sites
  • Brain Neoplasms/enzymology
  • Butyrylcholinesterase/genetics
  • Cholinesterase Inhibitors/pharmacology
  • DNA, Neoplasm/genetics
  • Dibucaine/pharmacology
  • Genetic Variation
  • Glioma/enzymology
  • Humans
  • Mutagenesis, Site-Directed
  • Neuroblastoma/enzymology
  • Recombinant Proteins/metabolism
  • Substrate Specificity
  • Succinylcholine/pharmacology


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