Sequence and phylogenetic analysis of viper venom serine proteases |
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Authors: | Sakthivel Vaiyapuri Nethaji Thiyagarajan E Gail Hutchinson Jonathan M Gibbins |
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Institution: | 1Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, United Kingdom;2Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom |
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Abstract: | Snakebites are a major neglected tropical disease responsible for as many as 95000 deaths every year worldwide. Viper venom
serine proteases disrupt haemostasis of prey and victims by affecting various stages of the blood coagulation system. A better
understanding of their sequence, structure, function and phylogenetic relationships will improve the knowledge on the
pathological conditions and aid in the development of novel therapeutics for treating snakebites. A large dataset for all available
viper venom serine proteases was developed and analysed to study various features of these enzymes. Despite the large number of
venom serine protease sequences available, only a small proportion of these have been functionally characterised. Although, they
share some of the common features such as a C-terminal extension, GWG motif and disulphide linkages, they vary widely between
each other in features such as isoelectric points, potential N-glycosylation sites and functional characteristics. Some of the serine
proteases contain substitutions for one or more of the critical residues in catalytic triad or primary specificity pockets. Phylogenetic
analysis clustered all the sequences in three major groups. The sequences with substitutions in catalytic triad or specificity pocket
clustered together in separate groups. Our study provides the most complete information on viper venom serine proteases to date
and improves the current knowledge on the sequence, structure, function and phylogenetic relationships of these enzymes. This
collective analysis of venom serine proteases will help in understanding the complexity of envenomation and potential therapeutic
avenues. |
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