Sequence and phylogenetic analysis of viper venom serine proteases

Abstract

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. Background:Snakebite is a major neglected public health issue particularly among agricultural communities living in rural regions throughout the world [1, 2]. An estimated 2.5 million people are bitten by snakes each year and these are estimated to result in up to as high as 95000 deaths worldwide . Snake venom serine proteases are major components and have been identified mainly in the venoms of snakes belonging to the viperidae family with a few occurring in members of the elapidae, colubridae and hydrophidae families [8]. Many snake venom serine proteases exert their effects through the ability to disrupt the normal haemostasis of envenomed prey and victims [9]. Indeed, viper venom serine proteases (VVSPs) affect various stages of the blood coagulation system, activate platelets and directly act upon fibrinogen. These include pro-coagulant

Exotic Snakebites Reported to Pennsylvania Poison Control Centers: Lessons Learned on the Demographics, Clinical Effects, and Treatment of These Cases

“…Elapid envenomation characteristically results in neurologic effects, whereas viper bites often present with hematological complications and local tissue injury. However, several of our cases demonstrate that clinical effects may overlap between these two families due to species-specific toxins [20]. For example, our case of the elapid, Naja pallida envenomation did report elevated prothrombin time and d-dimer level as well as thrombocytopenia.…”

Comprehensive Study of the Proteome and Transcriptome of the Venom of the Most Venomous European Viper: Discovery of a New Subclass of Ancestral Snake Venom Metalloproteinase Precursor-Derived Proteins

“…Vaa-SP-2 is a basic protein while Vaa-SP-3, Vaa-SP-4, Vaa-SP-5, and Vaa-SP-8 are acidic and Vaa-SP-6 and Vaa-SPH-1 neutral proteins. As is usual for viperid SVSPs, 39 the Vaa-SPs also possess various numbers of consensus N -glycosylation sites in their sequences, and thus have the potential of becoming N -glycosylated. Four such sites have been found in Vaa-SP-2 and Vaa-SP-6, three in Vaa-SP-4 and Vaa-SP-8, and two in each of Vaa-SP-3, Vaa-SP-5, and Vaa-SPH-1.…”

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

“…Snake Venom Serine Proteinases (SVSPs) belong to the S1 family of serine proteinases and display molecular masses ranging from 26 to 67 kDa and two distinct structural domains (Figure 3). These venom toxins have evolved from kallikreinlike serine proteases and, following their recruitment for use in the venom gland, have undergone gene duplication events giving rise to multiple isoforms (Fry et al, 2008;Vaiyapuri et al, 2012). SVSPs catalyze the cleavage of polypeptide chains on the C-terminal side of positively charged or hydrophobic amino acid residues (Page and Di Cera, 2008;Serrano, 2013).…”