Abstract
Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.
Highlights
Snake venom is a complex mixture of proteins and peptides, and presents several medical and pharmaceutical applications [1,2,3]
The venoms of snakes represent a large library of active compounds, and we have shown here how modern computational biology and chemistry are used in many aspects of their initial characterization, from the discovery of genes and proteins to the determination of their three-dimensional structure and interaction with molecular targets
We focused on the molecular modeling studies of Phospholipases A2 (PLA2), crotamine, and mambalgin, which were chosen as representative of the breadth of current computational techniques, but other important snake compounds have been studied by molecular modeling, e.g., α-bungarotoxin and other three-finger toxins targeting the nicotinic acetylcholine receptors [150]
Summary
Snake venom is a complex mixture of proteins and peptides, and presents several medical and pharmaceutical applications [1,2,3]. The most famous example of snake-derived medicine is captopril (Capoten), which was developed by Bristol-Myers Squibb, and is used as a generic medicine for treating hypertension and congestive heart failure [5,6] It is a small molecule inhibitor of the angiotensin converting enzyme (ACE), and is derived from bradykinin potentiating peptides found in the venom of the South American snake Bothrops jararaca [5]. Another snake-derived compound potentially used for heart failure is cenderitide (CD-NP, Mayo Clinic/Capricor Therapeutics, Beverly Hills, CA, USA) [7]. PLA2, the small basic myotoxin Crotamine and the three-finger peptide Mambalgin
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