%0 Journal Article
%T Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
%A Robin Doley
%A Stephen P Mackessy
%A R Manjunatha Kini
%J BMC Evolutionary Biology
%D 2009
%I BioMed Central
%R 10.1186/1471-2148-9-146
%X Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites.ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.Snake venoms contain a mixture of proteins and polypeptides which exhibit various biochemical and pharmacological functions. These proteins and polypeptides are classified into non-enzymatic and enzymatic proteins which belong to a small number of superfamilies, such as three-finger toxins (3FTx), Kunitz-type serine protease inhibitors, phospholipase A2(PLA2) enzymes, serine proteases and metalloproteases [1-12]. Members of these superfamilies have similar protein scaffolds but, at times, differ markedly in their biological effects. For example, members of 3FTx family exhibit a wide variety of specific pharmacologic effects by targeting various receptors and ion channels with high affinity and specificity. Short chain and long chain ¦Á-neuro
%U http://www.biomedcentral.com/1471-2148/9/146