Mk. Gentry et al., CHARACTERIZATION OF MONOCLONAL-ANTIBODIES THAT INHIBIT THE CATALYTIC ACTIVITY OF ACETYLCHOLINESTERASES, Journal of neurochemistry, 64(2), 1995, pp. 842-849
Monoclonal antibodies were generated against fetal bovine serum acetyl
cholinesterase and fetal bovine serum acetylcholinesterase inhibited b
y diisopropyl fluorophosphate or 7-(methyl ethoxyphosphinyloxy)-1-meth
ylquinolinium iodide. Six monoclonal antibodies inhibited 70 to >98% o
f the catalytic activity of fetal bovine serum acetylcholinesterase. I
nhibition of serum acetylcholinesterase from several mammalia by four
monoclonal antibodies showed broad cross-reactivity. In all cases, mon
oclonal antibodies bound to the native form of acetylcholinesterases.
None reacted with serum butyrylcholinesterases from various species. A
lthough all monoclonal antibodies inhibited catalytic activity of acet
ylcholinesterases, the site of interaction with acetylcholinesterase a
ppeared to differ for several antibodies. Two types of acetylcholinest
erase:monoclonal antibody complexes were formed: one between tetrameri
c forms and another between catalytic subunits within the tetramer. Mo
noclonal antibodies that inhibited acetylcholinesterase activity at >9
8% also considerably slowed binding of diisopropyl fluorophosphate and
other organophosphorus compounds to the acetylcholinesterase:monoclon
al antibody complex. Binding of these monoclonal antibodies to acetylc
holinesterase influenced function of the enzyme's peripheral anionic s
ite. None of the antibodies bound to the esteratic site of acetylcholi
nesterase. Monoclonal antibodies caused changes in catalytic activity
of acetylcholinesterase by interaction at a site remote from the catal
ytic site, presumably at the entrance to the active site gorge.