ACETYLCHOLINESTERASE INHIBITION BY FASCICULIN - CRYSTAL-STRUCTURE OF THE COMPLEX

The crystal structure of the snake toxin fasciculin, bound to mouse ac etylcholinesterase (mAChE), at 3.2 Angstrom resolution reveals a syner gistic three-point anchorage consistent with the picomolar dissociatio n constant of the complex. Loop II of fasciculin contains a cluster of hydrophobic residues that interact with the peripheral anionic site o f the enzyme and sterically occlude substrate access to the catalytic site. Loop I fits in a crevice near the lip of the gorge to maximize t he surface area of contact of loop II at the gorge entry. The fascicul in core surrounds a protruding loop on the enzyme surface and stabiliz es the whole assembly. Upon binding of fasciculin, subtle structural r earrangements of AChE occur that could explain the observed residual c atalytic activity of the fasciculin-enzyme complex.