Structural insights into AChE inhibition by monoclonal antibodies

The target sites of three inhibitory monoclonal antibodies, Elec403, 408 and 410, on eel AChE have been defined previously. Elec403 and 410 are directed toward distinct but overlapping epitopes at the enzyme peripheral site, while Elec408 binds to a distinct regulatory site on the enzyme surface, where the "back door" may be located. Elec410 also inhibits Bunganus fasciatus AChE. To investigate the molecular determinants for AChE inhibition by these antibodies, we have cloned and sequenced the IgGs, generated, purified, characterized the Fab molecules, and initiated crystallographic and theoretical modeling studies. Preliminary data are presented.