Functional architectures of animal toxins: a clue to drug design?
Toxic proteins are produced by a diversity of venomous animals from various 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 channels. The aim of this brief and non-exhaustive review is three-fold. First, the structural context associated with the functional diversity of animal toxins is presented. Among various situations, it is shown that toxins with a similar fold can exert different functions and that toxins with unrelated folds can exert similar functions. Second, the functional sites of some animal toxins are presented. Their comparison shed light on how (i) distinct functions can be exerted by similarly folded toxins and (ii) similar functions can be shared by structurally distinct toxins. Third, it is shown that part of the functional site of foreign proteins can be grafted on an animal toxin scaffold, opening new perspectives in the domain of protein engineering.
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Département d'Ingénierie et d'Etudes des Protéines, CEA Saclay, Gif-sur-Yvette, France.
D000818:Animals; D002038:Bungarotoxins / Q000737:chemistry / Q000633:toxicity; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry / Q000633:toxicity; D003463:Cues; D015195:Drug Design; D004546:Elapid Venoms / Q000737:chemistry / Q000633:toxicity; D008958:Models, Molecular; D008974:Mollusca; D011487:Protein Conformation; D012605:Scorpions; D012911:Snakes; D014118:Toxins, Biological / Q000737:chemistry* / Q000633:toxicity
D002038:Bungarotoxins; D003039:Cobra Neurotoxin Proteins; D004546:Elapid Venoms; D014118:Toxins, Biological; C025154:alpha-cobratoxin; C044937:fasciculin