Crystal structure of bucain, a three-fingered toxin from the venom of the Malayan krait (Bungarus candidus).

Bucain, a potent neurotoxin isolated from the venom of the Malayan krait (Bungarus candidus), induces paralysis and death. Its crystal structure has been determined at 2.10 A resolution and based on the molecular topology and hydrophobicity profile is structurally classified as a three-fingered alpha-neurotoxin possessing a positively charged AChR-binding site.

Comparative study of the inhibitory effect of antidepressants on cholinesterase activity in Bungarus sindanus (krait) venom, human serum and rat striatum.

Cholinesterases are divided into two classes based on differences in their substrate specificity and tissue distribution: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes may be inhibited by several compounds, such as antidepressants. The antidepressants paroxetine, imipramine, clomipramine and sertraline inhibited both venom AChE as well as human serum BChE in a concentration-dependent manner but had no effect on AChE in the rat brain striatum. The IC(50) of venom calculated for imipramine was 0.3 mM, paroxetine 0.38 mM, clomipramine 0.34 mM and sertraline 0.35 mM. Analysis of kinetic data indicated that the inhibition caused by sertraline and paroxetine was mixed, i.e. K(m) values increased and V(max) decreased in a concentration dependent manner. Imipramine and clomipramine exhibited competitive inhibition, i.e. K(m) values increased and V(max) remained constant. The present results suggest that these therapeutic agents used for depression can also be considered as inhibitors of snake venom and human serum cholinesterase.