Characterization of monoclonal antibodies that inhibit the catalytic activity of acetylcholinesterases.
Monoclonal antibodies were generated against fetal bovine serum acetylcholinesterase and fetal bovine serum acetylcholinesterase inhibited by diisopropyl fluorophosphate or 7-(methylethoxyphosphinyloxy)-1-methylquinolinium iodide. Six monoclonal antibodies inhibited 70 to > 98% of the catalytic activity of fetal bovine serum acetylcholinesterase. Inhibition of serum acetylcholinesterase from several mammalia by four monoclonal antibodies showed broad cross-reactivity. In all cases, monoclonal antibodies bound to the native form of acetylcholinesterases. None reacted with serum butyrylcholinesterases from various species. Although all monoclonal antibodies inhibited catalytic activity of acetylcholinesterases, the site of interaction with acetylcholinesterase appeared to differ for several antibodies. Two types of acetylcholinesterase:monoclonal antibody complexes were formed: one between tetrameric forms and another between catalytic subunits within the tetramer. Monoclonal antibodies that inhibited acetylcholinesterase activity at > 98% also considerably slowed binding of diisopropyl fluorophosphate and other organophosphorus compounds to the acetylcholinesterase:monoclonal antibody complex. Binding of these monoclonal antibodies to acetylcholinesterase influenced function of the enzyme's peripheral anionic site. None of the antibodies bound to the esteratic site of acetylcholinesterase. Monoclonal antibodies caused changes in catalytic activity of acetylcholinesterase by interaction at a site remote from the catalytic site, presumably at the entrance to the active site gorge.
Gentry
M K
MK
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Moorad
D R
DR
Hur
R S
RS
Saxena
A
A
Ashani
Y
Y
Doctor
B P
BP
D000110:Acetylcholinesterase / Q000097:blood* / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D002384:Catalysis; D002417:Cattle; D002800:Cholinesterase Inhibitors; D005312:Fetal Blood; D008322:Mammals / Q000097:blood; D009943:Organophosphorus Compounds / Q000276:immunology; D010091:Oximes / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D010091:Oximes; D000110:Acetylcholinesterase