Privileged frameworks from snake venom

Abstract

Venom as a form of chemical prey capture is a key innovation that has underpinned the explosive radiation of the advanced snakes (Caenophidia). Small venom proteins are often rich in disulfide bonds thus facilitating stable molecular scaffolds that present key functional residues on the protein surface. New toxin types are initially developed through the venom gland over-expression of normal body proteins, their subsequent gene duplication and diversification that leads to neofunctionalisation as random mutations modify their structure and function. This process has led to preferentially selected (privileged) cysteine-rich scaffolds that enable the snake to build arrays of toxins many of which may lead to therapeutic products and research tools. This review focuses on cysteine-rich small proteins and peptides found in snake venoms spanning natriuretic peptides to phospholipase enzymes, while highlighting their three-dimensional structures and biological functions as well as their potential as therapeutic agents or research tools.

Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation

“…The majority of this research has centered on antivenom investigation, but as the last 20 years of research has shown, snake venom also provides insights into evolutionary and ecological adaptations and is a largely untapped source of compounds with potential as research tools or therapeutics [63]. The advent of high throughput NGS…”

“…Unraveling the complexity of snake venoms has largely been dependent upon advances in separation technologies combined with modern proteomic analysis [2].…”

“…Elapid venoms contain numerous protein and peptide families that act as enzymes or ligands of membrane bound receptors with agonist or inhibitory mechanisms of action [1]. A number of families, such as the phospholipase A 2 (PLA 2 ) enzymes, and three finger toxins (3FTxs) exhibit conserved structural frameworks that present a broad range of pharmacological effects [2]. Diversity of function within each protein family is a key attribute of snake venom [3].…”

“…Additionally, complexes of PLA 2 toxins, such as textilotoxin, are capable of producing highly neurotoxic effects [4].…”

Protein-species quantitative venomics: looking through a crystal ball

“…Among these elements, sulfur results of particular relevance in proteomics (and specifically in venomics). Incorporated into the amino acids methionine and cysteine, the element sulfur is present in almost all toxin classes, particularly in small proteins whose global folds are stabilized primarily by the formation of disulfide bonds [44]. Mass spectrometric determination of cysteine (in SH and S–S forms) content represents a useful proxy for the preliminary classification of toxins into protein families [45].…”