Snake Venom Metalloproteinases

Abstract

As more data are generated from proteome and transcriptome analysis revealing that metalloproteinases represent most of the Viperid and Colubrid venom components authors decided to describe in a short review a classification and some of the multiple activities of snake venom metalloproteinases. SVMPs are classified in three major classes (P-I, P-II and P-III classes) based on the presence of various domain structures and according to their domain organization. Furthermore, P-II and P-III classes were separated in subclasses based on distinctive post-translational modifications. SVMPs are synthesized in a latent form, being activated through a Cys-switch mechanism similar to matrix metalloproteinases. Most of the metalloproteinases of the snake venom are responsible for the hemorrhagic events but also have fibrinogenolytic activity, poses apoptotic activity, activate blood coagulation factor II and X, inhibit platelet aggregation, demonstrating that SVMPs have multiple functions in addition to well-known hemorrhagic function.Keywords: snake venom metalloproteinases, hemorrhagic activity, hemostatic distruption, ADAM and ADAMTS, SVMPs IntroductionSnakes have fascinated humankind for millennia, being worshiped in antiquity by almost all the civilizations. In Ancient Egypt a Cobra adorned the pharaoh's crown, in Greece snakes could be found in many medical symbols, while in India snakes even had their own festival (Nag Panchami) [1,2].The destructive effect of snake venom on living organism was well known, but their healing potential has only been considered in the last 2 centuries. Snake venoms are typically a complex cocktail of mostly peptides, proteins, enzymes and other small substances with toxic and lethal properties that facilitate the immobilization and digestion of the prey, as well as providing a defense against predators. The life or death of these prey/predator encounters forced the toxins to be fast-acting and potent molecules. The most common snake venom enzymes include; cysteine-rich secretory proteins (CRiSPs), three-finger toxins (3FTXs) especially in Elapidae family, phospholipase A 2 , metalloproteinases, L-amino acid oxidase, serine proteinases, acetylcholinesterase, and phosphodiesterase [3]. HistoryEarly studies by Reichert and Mitchell noticed that fibrinogen in animal blood loses its ability to coagulate after exposure to snake venom. They observed that when animal blood was mixed with Crotalus family venom, the blood clot that was formed was dissolved within 24 hours while sitting at room temperature [4,5]. Probably the first report of SVMPs was by Ohsaka, Okonogi and Maeno when they observed that isolated proteinases toxin from viperid were inactivated by exposure to EDTA, presumably because of the presence of a metal inside the protein, most likely being a metalloproteinase [6][7][8][9].Since the discovery of zinc-dependent proteinase in the viperid venom [10], researchers have tried to isolate, characterize and understand the structure and biological function in order to find their role...

Exploring Toxin Genes of Myanmar Russell’s Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics

“…Snake venom metalloproteinases (SVMPs) are zinc endopeptidases varying from 20 to 100 kDa. They are the major components of viper venom, varying from 11% to 65% of the whole venom cocktail [ 61 , 62 ]. SVMPs have sequence and domain similarities to ADAM (A disintegrin and metalloproteinase) and can be grouped into three major classes (PI-PIII) according to their organization [ 53 , 63 ].…”

“…SVMPs have sequence and domain similarities to ADAM (A disintegrin and metalloproteinase) and can be grouped into three major classes (PI-PIII) according to their organization [ 53 , 63 ]. SVMPs are responsible for local and systemic hemorrhage, myonecrosis, the disruption of hemostasis mediated by procoagulant or anticoagulant effects or platelet aggregation, tissue necrosis and pro-inflammation [ 61 ]. These activities are mediated by metalloproteinase, disintegrin and/or disintegrin-like domains [ 62 ].…”

“…The structure and biological activity of DSAIP still needs to be elucidated. RVV-X and daborhagin are found in both Myanmar and Indian RV species, while VRR-73, VRH-1 and RVBCMP are from only Indian RV [ 61 ]. Daborhagin-M is a P-IIIc hemorrhagic SVMP with high proteolytic activity toward fibrinogen, fibronectin and collagen [ 67 ].…”

Protease Activity Profiling of Snake Venoms Using High-Throughput Peptide Screening

“…These enzymes are known to affect a large number of physiological pathways and response cascades, assisting in immobilization and death. In addition, venom proteinases play a role in digesting prey, as well as deterring predators [7]. Proteinases have the ability to cleave other proteins by the hydrolysis of peptide bonds, whereby these other proteins may become activated or deactivated.…”