An inhibitory monoclonal antibody to rabbit brain acetylcholinesterase. Studies on interaction with the enzyme

S. Brimijoin, K. P. Mintz, F. G. Prendergast

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

A recently isolated monoclonal antibody was found to be a potent and powerful inhibitor of the catalytic activity of rabbit brain acetylcholinesterase (AChE; acetylcholine acetylhydrolase, EC 3.1.1.7), with an IC50 of about 1 nM and a maximal inhibition of at least 90%. The antibody increased the optimal concentration of acetylthiocholine as much as 50-fold, but analysis of the substrate kinetics did not indicate a simple competitive interaction. The antibody markedly reduced the labeling of purified rabbit brain AChE by tritiated diisopropyl fluorophosphate (DFP) and also impeded the binding of propidium iodide, a fluorescent probe thought to be directed toward the peripheral anionic site. The antibody's affinity for enzyme with active sites that were phosphorylated with DFP or occupied by reversible ligands was measurably less than for native enzyme. It is possible that the mechanism of inhibition involves antibody-induced conformational changes that are unfavorable for catalysis.

Original languageEnglish (US)
Pages (from-to)539-545
Number of pages7
JournalMolecular pharmacology
Volume28
Issue number6
StatePublished - Dec 1 1985

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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