title: Structure, function and evolution of three-finger toxins: mini proteins with multiple targets.
abstract: Snake venoms are complex mixtures of pharmacologically active peptides and proteins. These protein toxins belong to a small number of superfamilies of proteins. Three-finger toxins belong to a superfamily of non-enzymatic proteins found in all families of snakes. They have a common structure of three beta-stranded loops extending from a central core containing all four conserved disulphide bonds. Despite the common scaffold, they bind to different receptors/acceptors and exhibit a wide variety of biological effects. Thus, the structure-function relationships of this group of toxins are complicated and challenging. Studies have shown that the functional sites in these 'sibling' toxins are located on various segments of the molecular surface. Targeting to a wide variety of receptors and ion channels and hence distinct functions in this group of mini proteins is achieved through a combination of accelerated rate of exchange of segments as well as point mutations in exons. In this review, we describe the structural and functional diversity, structure-function relationships and evolution of this group of snake venom toxins.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore. dbskinim@nus.edu.sg
authors.forename: R Manjunatha
authors.initials: RM
authors.lastname: Kini
authors.forename: Robin
authors.initials: R
authors.lastname: Doley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000737:chemistry; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D012910:Snake Venoms / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004220:Disulfides; D009498:Neurotoxins; D012910:Snake Venoms