FUNCTIONAL ARCHITECTURES OF ANIMAL TOXINS - A CLUE TO DRUG DESIGN

Toxic proteins are produced by a diversity of venomous animals from va rious phyla. They are often of small size, possess a large density of disulfide bonds and exert multiple functions directed toward a variety of molecular targets, including a diversity of enzymes and ion channe ls. The aim of this brief and non-exhaustive review is three-fold. Fir st, the structural context associated with the functional diversity of animal toxins is presented. Among various situations, it is shown tha t toxins with a similar fold can exert different functions and that to xins with unrelated folds can exert similar functions. Second, the fun ctional sites of some animal toxins are presented. Their comparison sh ed light on how (i) distinct functions can be exerted by similarly fol ded toxins and (ii) similar functions can be shared by structurally di stinct toxins. Third, it is shown that part of the functional site of foreign proteins can be grafted on an animal toxin scaffold, opening n ew perspectives in the domain of protein engineering. (C) 1998 Publish ed by Elsevier Science Ltd. All rights reserved.