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141  structures 92  species 2  interactions 594  sequences 1  architecture

Family: Toxin_1 (PF00087)

Summary: Snake toxin

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Snake toxin
Identifiers
Symbol Toxin_1
Pfam PF00087
InterPro IPR003571
PROSITE PDOC00245
SCOP 2ctx
SUPERFAMILY 2ctx
OPM superfamily 55
OPM protein 1txa

Snake venom is highly modified saliva[1] containing zootoxins that facilitates the immobilization and digestion of prey, and defends against a threat. It is injected by unique fangs after a bite but some species are also able to spit.[2]

The glands that secrete the zootoxins are a modification of the parotid salivary gland found in other vertebrates and are usually situated on each side of the head, below and behind the eye and encapsulated in a muscular sheath. The glands have large alveoli in which the synthesized venom is stored before being conveyed by a duct to the base of channeled or tubular fangs through which it is ejected.[3][4]

Venoms contain more than 20 different compounds, mostly proteins and polypeptides.[3] A complex mixture of proteins, enzymes, and various other substances with toxic and lethal properties[2] serves to immobilize the prey animal,[5] enzymes play an important role in the digestion of prey,[4] and various other substances are responsible for important but non-lethal biological effects.[2] Some of the proteins in snake venom have very specific effects on various biological functions including blood coagulation, blood pressure regulation, transmission of the nervous or muscular impulse and have been developed for use as pharmacological or diagnostic tools or even useful drugs.[2]

Chemistry

Charles Lucien Bonaparte, the son of Lucien Bonaparte, younger brother of Napoleon Bonaparte, was the first to establish the proteinaceous nature of snake venom in 1843.

Proteins constitute 90-95% of venom's dry weight and they are responsible for almost all of its biological effects. Among hundreds, even thousands of proteins found in venom, there are toxins, neurotoxins in particular, as well as nontoxic proteins (which also have pharmacological properties), and many enzymes, especially hydrolytic ones.[2] Enzymes (molecular weight 13-150 KDa) make-up 80-90% of viperid and 25-70% of elapid venoms: digestive hydrolases, L-amino acid oxidase, phospholipases, thrombin-like pro-coagulant, and kallikrein-like serine proteases and metalloproteinases (hemorrhagins), which damage vascular endothelium. Polypeptide toxins (molecular weight 5-10 KDa) include cytotoxins, cardiotoxins, and postsynaptic neurotoxins (such as α-bungarotoxin and α-Cobratoxin), which bind to acetylcholine receptors at neuromuscular junctions. Compounds with low molecular weight (up to 1.5 KDa) include metals, peptides, lipids, nucleosides, carbohydrates, amines, and oligopeptides, which inhibit angiotensin converting enzyme (ACE) and potentiate bradykinin (BPP). Inter- and intra-species variation in venom chemical composition is geographical and ontogenic.[3] Phosphodiesterases interfere with the prey's cardiac system, mainly to lower the blood pressure. Phospholipase A2 causes hemolysis by lysing the phospholipid cell membranes of red blood cells.[6] Amino acid oxidases and proteases are used for digestion. Amino acid oxidase also triggers some other enzymes and is responsible for the yellow colour of the venom of some species. Hyaluronidase increases tissue permeability to accelerate absorption of other enzymes into tissues. Some snake venoms carry fasciculins, like the mambas (Dendroaspis), which inhibit cholinesterase to make the prey lose muscle control.[7]

Main Enzymes of Snake Venom[2]
Type Name Origin
Oxydoreductases dehydrogenase lactate Elapidae
L-amino-acid oxidase All species
Catalase All species
Transferases Alanine amino transferase
Hydrolases Phospholipase A2 All species
Lysophospholipase Elapidae, Viperidae
Acetylcholinesterase Elapidae
Alkaline phosphatase Bothrops atrox
Acid phosphatase Deinagkistrodon acutus
5'-Nucleotidase All species
Phosphodiesterase All species
Deoxyribonuclease All species
Ribonuclease 1 All species
Adenosine triphosphatase All species
Amylase All species
Hyaluronidase All species
NAD-Nucleotidase All species
Kininogenase Viperidae
Factor-X activator Viperidae, Crotalinae
Heparinase Crotalinae
α-Fibrinogenase Viperidae, Crotalinae
β-Fibrinogenase Viperidae, Crotalinae
α-β-Fibrinogenase Bitis gabonica
Fibrinolytic enzyme Crotalinae
Prothrombin activator Crotalinae
Collagenase Viperidae
Elastase Viperidae
Lyases Glucosamine ammonium lyase

Snake toxins vary greatly in their functions. Two broad classes of toxins found in snake venoms are neurotoxins (mostly found in elapids) and hemotoxins (mostly found in viperids). However, there are exceptions - the venom of the black-necked spitting cobra (Naja nigricollis) consists mainly of hemotoxins, while that of the Mojave rattlesnake (Crotalus scutulatus) is primarily neurotoxic. There are numerous other types of toxin which both elapids and viperids may carry.

α-neurotoxins α-Bungarotoxin, α-toxin, erabutoxin, cobratoxin
β-neurotoxins Notexin, ammodytoxin, β-Bungarotoxin, crotoxin, taipoxin
κ-Toxins κ-Toxin
Dendrotoxins Dendrotoxin, toxins I and K
Cardiotoxins y-Toxin, cardiotoxin, cytotoxin
Myotoxins Myotoxin-a, crotamine
Sarafotoxins Sarafotoxins a, b, and c
Hemorrhagins Phospholipase A2, mucrotoxin A, hemorrhagic toxins a, b, c..., HT1, HT2

Toxins

Neurotoxins

Structure of a typical chemical synapse

The beginning of a new impulse:

A) An exchange of ions (charged atoms) across the nerve cell membrane sends a depolarizing current towards the end of the nerve cell (cell terminus).

B) When the depolarizing current arrives at the nerve cell terminus, the neurotransmitter acetylcholine (ACh), which is held in vesicles, is released into the space between the two nerves (synapse). It moves across the synapse to the postsynaptic receptors.

C) ACh binds to the receptors and transfers the signal to the target cell, after a short time it is destroyed by acetylcholinesterase. If multiple stimuli come from the nerve the same thing will happen many more times and then its called a tetanus which is a normal thing for muscles, it's how they work.

Fasciculins:

These toxins attack cholinergic neurons (those that use ACh as a transmitter) by destroying acetylcholinesterase (AChE). ACh therefore cannot be broken down and stays in the receptor. This causes tetany (involuntary muscle contraction), which can lead to death. The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting (5-7 h) fasciculations (rapid muscle contractions).

Snake example: found mostly in venom of mambas (Dendroaspis spp.) and some rattlesnakes (Crotalus spp.)

Dendrotoxins:

Dendrotoxins inhibit neurotransmissions by blocking the exchange of positive and negative ions across the neuronal membrane lead to no nerve impulse, thereby paralysing the nerves.

Snake example: mambas

α-neurotoxins:

This is a large group of toxins, with over 100 postsynaptic neurotoxins having been identified and sequenced.[8] α-neurotoxins also attack cholinergic neurons. They mimic the shape of the acetylcholine molecule and therefore fit into the receptors → they block the ACh flow → feeling of numbness and paralysis.

Snake examples: king cobra (Ophiophagus hannah) (known as hannahtoxin containing α-neurotoxins),[9] sea snakes (Hydrophiinae) (known as erabutoxin), many-banded krait (Bungarus multicinctus) (known as α-Bungarotoxin), and cobras (Naja spp.) (known as cobratoxin)

Cytotoxins

Fully functional membrane

Phospholipases:

Phospholipase is an enzyme that transforms the phospholipid molecule into a lysophospholipid (soap) ==> the new molecule attracts and binds fat and ruptures cell membranes.

Snake example: Okinawan habu (Trimeresurus flavoviridis)

Destroyed membrane

Cardiotoxins:

Cardiotoxins are components that are specifically toxic to the heart. They bind to particular sites on the surface of muscle cells and cause depolarisation ==> the toxin prevents muscle contraction. These toxins may cause the heart to beat irregularly or stop beating, causing death.

Snake example: mambas, and some cobra species

Hemotoxins:

Hemotoxins cause hemolysis, the destruction of red blood cells (erythrocytes), or induce blood coagulation (clotting).

Snake example: most vipers and many cobra species. The tropical rattlesnake Crotalus durissusproduces convulxin, a coagulant.[10]

Snake cytotoxin IPR003572

Determining venom toxicity (LD50)

The potency of the venom of wild snakes varies considerably, even within any single species. This is because of assorted influences such as biophysical environment, physiological status, ecological variables, genetic variation (either adaptive or incidental) and various other molecular- and ecological evolutionary factors. Such variation necessarily is smaller in captive populations in controlled laboratory settings though it cannot be eliminated altogether. However, studies to determine snake venom lethality or potency need to be designed to minimise variability and several techniques have been designed to this end. One approach that is considered particularly helpful is to use 0.1% bovine serum albumin (also known as "Fraction V" in Cohn process) as a diluent in determining LD50 values for various species. It results in far more accurate and consistent median lethal dose (LD50) determinations than for example using 0.1% saline as a diluent. Fraction V produces about 95% purified albumin, which is the dried crude venom. Saline as a diluent consistently produces widely varying LD50 results for nearly all venomous snakes; it produces unpredictable variation in the purity of the precipitate (range from 35-60%).[11] Fraction V is structurally stable because it has seventeen disulfide bonds; it is unique in that it has the highest solubility and lowest isoelectric point of all the major plasma proteins. This makes it the final fraction to be precipitated from its solution. Bovine serum albumin is located in fraction V. The precipitation of albumin is done by reducing the pH to 4.8, which is near the pI of the proteins, and maintaining the ethanol concentration to be 40%, with a protein concentration of 1%. Thus, only 1% of the original plasma remains in the fifth fraction.[12] When the ultimate goal of plasma processing is a purified plasma component for injection or transfusion, the plasma component must be highly pure. The first practical large-scale method of blood plasma fractionation was developed by Edwin J. Cohn during World War II. It is known as the Cohn process (or Cohn method). This process is also known as cold ethanol fractionation as it involves gradually increasing the concentration of ethanol in the solution at 5oC and 3oC.[13] The Cohn Process exploits differences in properties of the various plasma proteins, specifically, the high solubility and low pI of albumin. As the ethanol concentration is increased in stages from 0% to 40% the [pH] is lowered from neutral (pH ~ 7) to about 4.8, which is near the pI of albumin.[13] At each stage certain proteins are precipitated out of the solution and removed. The final precipitate is purified albumin. Several variations to this process exist, including an adapted method by Nitschmann and Kistler that uses less steps, and replaces centrifugation and bulk freezing with filtration and diafiltration.[13][14] Some newer methods of albumin purification add additional purification steps to the Cohn Process and its variations. Chromatographic albumin processing as an alternative to the Cohn Process emerged in the early 1980s, however, it was not widely adopted until later due to the inadequate availability of large scale chromatography equipment. Methods incorporating chromatography generally begin with cryo-depleted plasma undergoing buffer exchange via either diafiltration or buffer exchange chromatography, to prepare the plasma for following ion exchange chromatography steps. After ion exchange there are generally further chromatographic purification steps and buffer exchange.[13]

However, chromatographic methods for separation started being adopted in the early 1980s. Developments were ongoing in the time period between when Cohn fractionation started being used, in 1946, and when chromatography started being used, in 1983. In 1962, the Kistler & Nistchmann process was created which was a spin-off of the Cohn process. Chromatographic processes began to take shape in 1983. In the 1990s, the Zenalb and the CSL Albumex processes were created which incorporated chromatography with a few variations. The general approach to using chromatography for plasma fractionation for albumin is: recovery of supernatant I, delipidation, anion exchange chromatography, cation exchange chromatography, and gel filtration chromatography. The recovered purified material is formulated with combinations of sodium octanoate and sodium N-acetyl tryptophanate and then subjected to viral inactivation procedures, including pasteurisation at 60 °C. This is a more efficient alternative than the Cohn process for four main reasons: 1) smooth automation and a relatively inexpensive plant was needed, 2) easier to sterilize equipment and maintain a good manufacturing environment, 3) chromatographic processes are less damaging to the albumin protein, and 4) a more successful albumin end result can be achieved. Compared with the Cohn process, the albumin purity went up from about 95% to 98% using chromatography, and the yield increased from about 65% to 85%. Small percentage increases make a difference in regard to sensitive measurements like purity. There is one big drawback in using chromatography, which has to do with the economics of the process. Although the method was efficient from the processing aspect, acquiring the necessary equipment is a big task. Large machinery is necessary, and for a long time the lack of equipment availability was not conducive to its widespread use. The components are more readily available now but it is still a work in progress.

Evolution

Snake venom consists of many different toxin proteins: these can either have enzymatic activity, which typically assists in digestion, or can be shorter peptides that are used to immobilize prey.[15] Toxin proteins make up many multigene families, and arose from gene recruitment of proteins that do not code for toxins, followed by extensive evolutionary modification.[16][17][18] Toxin evolution follows the birth-and-death model of gene families, where duplication followed by functional diversification results in the creation of structurally related proteins that have slightly different functions. It is thought that venom as a way to immobilize prey was beneficial in allowing the uncoupling of feeding system and locomotion, which are coupled in the Haenophidians, which then enabled snakes with venom systems to colonize open areas.[19] Venom continue to evolve as specific toxins are modified to target a specific prey, and it is found that toxins vary according to diet in some species.[20][21]

The presence of enzymes in snake venom was once believed to be an adaptation to assist digestion. However, studies of the western diamondback rattlesnake (Crotalus atrox), a snake with highly proteolytic venom, show that venom has no impact on the time required for food to pass through the gut.[22]

Injection

Vipers

In the vipers, which have the most highly developed venom delivery apparatus, the venom gland is very large and is surrounded by the masseter or temporal muscle, which consists of two bands, the superior arising from behind the eye, the inferior extending from the gland to the mandible. A duct carries venom from the gland to the fang. In vipers and elapids, this groove is completely closed, forming a hypodermic needle-like tube. In other species, the grooves are not covered, or only partially covered. From the anterior extremity of the gland, the duct passes below the eye and above the maxillary bone, to the basal orifice of the venom fang, which is ensheathed in a thick fold of mucous membrane. By means of the movable maxillary bone hinged to the prefrontal bone and connected with the tranverse bone which is pushed forward by muscles set in action by the opening of the mouth, the fang is erected and the venom discharged through the distal orifice. When the snake bites, the jaws close and the muscles surrounding the gland contract, causing venom to be ejected via the fangs.

Elapids

In the proteroglyphous elapids, the fangs are tubular, but are short and do not possess the mobility seen in vipers.

Colubrids

Opisthoglyphous colubrids have enlarged, grooved teeth situated at the posterior extremity of the maxilla, where a small posterior portion of the upper labial or salivary gland produces venom.

Mechanics of biting

European adder (Vipera berus), one fang with a small venom stain in glove, the other still in place

Several genera, including Asian coral snakes (Calliophis), burrowing asps (Atractaspis) and night adders (Causus), are remarkable for having exceptionally long venom glands, extending along each side of the body, in some cases extending posterially as far as the heart. Instead of the muscles of the temporal region serving to press out the venom into the duct, this action is performed by those of the side of the body.

There is considerable variability in biting behavior among snakes. When biting, viperid snakes often strike quickly, discharging venom as the fangs penetrate the skin, and then immediately release. Alternatively, as in the case of a feeding response, some viperids (e.g. Lachesis) will bite and hold. A proteroglyph or opisthoglyph may close its jaws and bite or chew firmly for a considerable time.

Mechanics of spitting

Spitting cobras of the genera Naja and Hemachatus, when irritated or threatened, may eject streams or a spray of venom a distance of 4 to 8 feet. These snakes' fangs have been modified for the purposes of spitting: inside the fangs, the channel makes a ninety degree bend to the lower front of the fang. Spitters may spit repeatedly and still be able to deliver a fatal bite.

Spitting is a defensive reaction only. The snakes tend to aim for the eyes of a perceived threat. A direct hit can cause temporary shock and blindness through severe inflammation of the cornea and conjunctiva. Although usually there are no serious results if the venom is washed away immediately with plenty of water, blindness can become permanent if left untreated. Brief contact with the skin is not immediately dangerous, but open wounds may be vectors for envenomation.

Physiological effects

There are four distinct types of venom that act on the body differently.

  • Proteolytic venom dismantles the molecular structure of the area surrounding and including the bite.
  • Hemotoxic venoms act on the heart and cardiovascular system.
  • Neurotoxic venom acts on the nervous system and brain.
  • Cytotoxic venom has a localized action at the site of the bite.

It is noteworthy that the size of the venom fangs is in no relation to the virulence of the venom.

Proteroglyphous snakes

The effect of the venom of proteroglyphous snakes (sea snakes, kraits, mambas, black snakes, tiger snakes, death adders) is mainly on the nervous system, respiratory paralysis being quickly produced by bringing the venom into contact with the central nervous mechanism which controls respiration; the pain and local swelling which follow a bite are not usually severe.

The bite of all the proteroglyphous elapids, even of the smallest and gentlest, such as the coral snakes, is, so far as known, deadly to humans.

Vipers

Viper venom (Russell's viper, saw-scaled vipers, bushmasters, rattlesnakes) acts more on the vascular system, bringing about coagulation of the blood and clotting of the pulmonary arteries; its action on the nervous system is not great, no individual group of nerve-cells appears to be picked out, and the effect upon respiration is not so direct; the influence upon the circulation explains the great depression which is a symptom of viperine envenomation. The pain of the wound is severe, and is speedily followed by swelling and discoloration. The symptoms produced by the bite of the European vipers are thus described by Martin and Lamb:[23]

The bite is immediately followed by local pain of a burning character; the limb soon swells and becomes discoloured, and within one to three hours great prostration, accompanied by vomiting, and often diarrhoea, sets in. Cold, clammy perspiration is usual. The pulse becomes extremely feeble, and slight dyspnoea and restlessness may be seen. In severe cases, which occur mostly in children, the pulse may become imperceptible and the extremities cold; the patient may pass into coma. In from twelve to twenty-four hours these severe constitutional symptoms usually pass off; but in the meantime the swelling and discoloration have spread enormously. The limb becomes phlegmonous, and occasionally suppurates. Within a few days recovery usually occurs somewhat suddenly, but death may result from the severe depression or from the secondary effects of suppuration. That cases of death, in adults as well as in children, are not infrequent in some parts of the Continent is mentioned in the last chapter of this Introduction.

The Viperidae differ much among themselves in the toxicity of their venom. Some, such as the Indian Russell's viper (Daboia russelli) and saw-scaled viper (Echis carinatus); the American rattlesnakes (Crotalus spp.), bushmasters (Lachesis spp.) and lanceheads (Bothrops spp.); and the African adders (Bitis spp.), night adders (Causus spp.), and horned vipers (Cerastes spp.), cause fatal results unless a remedy is speedily applied. The bite of the larger European vipers may be very dangerous, and followed by fatal results, especially in children, at least in the hotter parts of the Continent; whilst the small meadow viper (Vipera ursinii), which hardly ever bites unless roughly handled, does not seem to be possessed of a very virulent venom, and, although very common in some parts of Austria and Hungary, is not known to have ever caused a serious accident.

Opisthoglyphous colubrids

Biologists had long known that some snakes had rear fangs, 'inferior' venom injection mechanisms that might immobilize prey; although a few fatalities were on record, until 1957 the possibility that such snakes were deadly to humans seemed at most remote. The deaths of two prominent herpetologists from African colubrid bites changed that assessment, and recent events reveal that several other species of rear-fanged snakes have venoms that are potentially lethal to large vertebrates.

Boomslang (Dispholidus typus) and twig snake (Thelotornis spp.) venom are toxic to blood cells and thin the blood (hemotoxic, hemorrhagic). Early symptoms include headaches, nausea, diarrhea, lethargy, mental disorientation, bruising and bleeding at the site and all body openings. Exsanguination is the main cause of death from such a bite.

The boomslang's venom is the most potent of all rear-fanged snakes in the world based on LD50. Although its venom may be more potent than some vipers and elapids, it causes fewer fatalities owing to various factors (for example, the fangs' effectiveness is not high compared with many other snakes: the venom dose delivered is low, and boomslangs are generally less aggressive in comparison to other venomous snakes such as cobras and mambas).

Symptoms of a bite from these snakes include nausea and internal bleeding, and one could die from a brain hemorrhage and respiratory collapse.

Aglyphous snakes

Experiments made with the secretion of the parotid gland of Rhabdophis and Zamenis have shown that even aglyphous snakes are not entirely devoid of venom, and point to the conclusion that the physiological difference between so-called harmless and venomous snakes is only one of degree, just as there are various steps in the transformation of an ordinary parotid gland into a venom gland or of a solid tooth into a tubular or grooved fang.

Use of snake venoms to treat disease

Given that snake venom contains many biologically ingredients, some may be useful to treat disease.[24]

For instance, Phospholipases type A2 (PLA2s) from the Tunisian vipers Cerastes cerastes and Macrovipera lebetina has been found to have anti-tumor activity.[25] Anti-cancer activity has been also reported for other compounds in snake venom.[26][27]

Phospholipases A2 hydrolyze phospholipids and thus could act on bacterial cell surfaces, providing novel antimicrobial (antibiotic) activities.[28]

The analgesic (pain-killing) activity of many snake venom proteins has been long known.[29][30] The main challenge, however, is to deliver protein to the nerve cells as proteins usually are not applicable as pills.

Immunity

Among snakes

The question whether individual snakes are immune to their own venom has not yet been definitively settled, though there is a known example of a cobra which self-envenomated, resulting in a large abscess requiring surgical intervention but showing none of the other effects that would have proven rapidly lethal in prey species or humans.[31] Furthermore, certain harmless species, such as the North American common kingsnake (Lampropeltis getula) and the Central and South American mussurana (Clelia spp.), are proof against the venom of the crotalines which frequent the same districts, and which they are able to overpower and feed upon. The chicken snake (Spilotes pullatus) is the enemy of the Fer-de-Lance (Bothrops caribbaeus) in St. Lucia, and it is said[by whom?] that in their encounters the chicken snake is invariably the victor. Repeated experiments have shown the European grass snake (Natrix natrix), not to be affected by the bite of European adder (Vipera berus) and European asp (Vipera aspis), this being due to the presence, in the blood of the harmless snake, of toxic principles secreted by the parotid and labial glands, and analogous to those of the venom of these vipers. Several North American species of rat snakes as well as king snakes have proven to be immune or highly resistant to the venom of rattlesnake species.

Among other animals

The hedgehog (Erinaceidae), the mongoose (Herpestidae), the honey badger (Mellivora capensis), the secretarybird (Sagittarius serpentarius) and a few other birds that feed on snakes are known to be immune to a dose of snake venom. Whether the pig may be considered so is still uncertain, although it is well known that, owing to its subcutaneous layer of fat, it is often bitten without ill effect. The garden dormouse (Eliomys quercinus) has recently been added to the list of animals refractory to viper venom. Some populations of California ground squirrel (Otospermophilus beecheyi) are at least partially immune to rattlesnake venom as adults.

Among humans

The acquisition of human immunity against snake venom is one of the oldest forms of vaccinology known to date (about AD 60, Psylli Tribe). Research into development of vaccines that will lead to immunity is ongoing. Bill Haast, owner and director of the Miami Serpentarium injected himself with snake venom during most of his adult life, in an effort to build up an immunity to a broad array of venomous snakes. It is a practice known as mithridatism. Haast lived to age 100, and survived a reported 172 snake bites. He donated his blood to be used in treating snake-bite victims when a suitable anti-venom was not available. More than twenty of those individuals recovered.[32][33][34]

Traditional Treatments

The World Health Organization estimates that 80% of the world’s population depends on traditional medicine for their primary health care needs.[35] Methods of traditional treatment of snake bite, although of questionable efficacy and perhaps even harmful, are nonetheless relevant.

Plants used to treat snakebites in Trinidad and Tobago are made into tinctures with alcohol or olive oil and kept in rum flasks called 'snake bottles'. Snake bottles contain several different plants and/or insects. The plants used include the vine called monkey ladder (Bauhinia cumanensis or Bauhinia excisa, Fabaceae) which is pounded and put on the bite. Alternatively a tincture is made with a piece of the vine and kept in a snake bottle. Other plants used include: mat root (Aristolochia rugosa), cat's claw (Pithecellobim unguis-cati), tobacco (Nicotiana tabacum), snake bush (Barleria lupulina), obie seed (Cola nitida), and wild gri gri root (Acrocomia aculeata). Some snake bottles also contain the caterpillars (Battus polydamas, Papilionidae) that eat tree leaves (Aristolochia trilobata). Emergency snake medicines are obtained by chewing a three-inch piece of the root of bois canôt (Cecropia peltata) and administering this chewed-root solution to the bitten subject (usually a hunting dog). This is a common native plant of Latin America and the Caribbean which makes it appropriate as an emergency remedy. Another native plant used is mardi gras (Renealmia alpinia)(berries), which are crushed together with the juice of wild cane (Costus scaber) and given to the bitten. Quick fixes have included applying chewed tobacco from cigarettes, cigars or pipes.[36] Making cuts around the puncture or sucking out the venom had been thought helpful, in the past, but this course of treatment is now strongly discouraged.[37][38]

Serotherapy

Especially noteworthy is progress regarding the defensive reaction by which the blood may be rendered proof against their effect, by processes similar to vaccination—antipoisonous serotherapy.

The studies to which we allude have not only conduced to a method of treatment against snake-bites, but have thrown a new light on the great problem of immunity.

They have shown that the antitoxic sera do not act as chemical antidotes in destroying the venom, but as physiological antidotes; that, in addition to the venom glands, snakes possess other glands supplying their blood with substances antagonistic to the venom, such as also exist in various animals refractory to snake venom, the hedgehog and the mongoose for instance.

Regional venom specificity

Unfortunately, the specificity of the different snake venoms is such that, even when the physiological action appears identical, serum injections or graduated direct inoculations confer immunity towards one species or a few allied species only.

Thus, a European in Australia who had become immune to the venom of the deadly Australian tiger snake (Notechis scutatus), manipulating these snakes with impunity, and was under the impression that his immunity extended also to other species, when bitten by a lowland copperhead (Austrelaps superbus), an allied elapine, died the following day.

In India, the serum prepared with the venom of monocled cobra Naja kaouthia has been found to be without effect on the venom of two species of kraits (Bungarus), Russell's viper (Daboia russelli), saw-scaled viper (Echis carinatus), and Pope's pit viper (Trimeresurus popeorum). Russell's viper serum is without effect on colubrine venoms, or those of Echis and Trimeresurus.

In Brazil, serum prepared with the venom of lanceheads (Bothrops spp.) is without action on rattlesnake (Crotalus spp.) venom.

Antivenom snakebite treatment must be matched as the type of envenomation that has occurred.

In the Americas, polyvalent antivenoms are available that are effective against the bites of most pit vipers. Crofab is the antivenom developed to treat the bite of North American pit-vipers.[39]

These are not effective against coral snake envenomation, which requires a specific antivenom to their neurotoxic venom.

The situation is even more complex in countries like India, with its rich mix of vipers (family Viperidae) and highly neurotoxic cobras and kraits of the family Elapidae.

This article is based on the 1913 book The Snakes of Europe, by G. A. Boulenger, which is now in the public domain in the United States (and possibly elsewhere). Because of its age, the text in this article should not necessarily be viewed as reflecting the current knowledge of snake venom.

See also

References

  1. ^ "Reptile Venom Research". Australian Reptile Park. Retrieved 21 December 2010. 
  2. ^ a b c d e f (Edited by) Bauchot, Roland (1994). Snakes: A Natural History. New York City, NY, USA: Sterling Publishing Co., Inc. pp. 194–209. ISBN 1-4027-3181-7. 
  3. ^ a b c (edited by) Halliday; Adler, Tim; Kraig (2002). Firefly Encyclopedia of Reptiles and Amphibians. Toronto, Canada: Firefly Books Ltd. pp. 202–203. ISBN 1-55297-613-0. 
  4. ^ a b Bottrall, Joshua L.; Frank Madaras; Christopher D Biven; Michael G Venning; Peter J Mirtschin (30 September 2010). "Proteolytic activity of Elapid and Viperid Snake venoms and its implication to digestion". Journal of Venom Research 1 (3): 18–28. PMC 3086185. PMID 21544178. Retrieved 26 December 2011. 
  5. ^ Mattison, Chris (2007 (first published in 1995)). The New Encyclopedia of Snakes. New Jersey, USA (first published in the UK): Princeton University Press (Princeton and Oxford) first published in Blandford. p. 117. ISBN 0-691-13295-X. 
  6. ^ Condrea, E.; De Vries, A.; Mager, J. (February 1964). "Hemolysis and splitting of human erythrocyte phospholipids by snake venoms". Biochimica et Biophysica Acta (BBA) - Specialized Section on Lipids and Related Subjects 84 (1): 60–73. doi:10.1016/0926-6542(64)90101-5. PMID 14124757.  Closed access
  7. ^ Rodríguez-Ithurralde, D.; R. Silveira; L. Barbeito; F. Dajas (1983). "Fasciculin, a powerful anticholinesterase polypeptide from Dendroaspis angusticeps venom". Neurochemistry International 5 (3): 267–274. doi:10.1016/0197-0186(83)90028-1.  Closed access
  8. ^ Hodgson, Wayne C.; Wickramaratna, Janith C. (September 2002). "In vitro neuromuscular activity of snake venoms". Clinical and Experimental Pharmacology and Physiology 29 (9): 807–814. doi:10.1046/j.1440-1681.2002.03740.x. PMID 12165047.  Closed access
  9. ^ He, Ying-Ying; Lee, Wei-Hui; Zhang, Yun (September 2004). "Cloning and purification of α-neurotoxins from king cobra (Ophiophagus hannah)". Toxicon 44 (3): 295–303. doi:10.1016/j.toxicon.2004.06.003. PMID 15302536.  Closed access
  10. ^ Hermans, C.; Wittevrongel, C.; Thys, C.; Smethurst, P. A.; Van Geet, C.; Freson, K. (August 2009). "A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder". Journal of Thrombosis and Haemostasis 7 (8): 1356–1363. doi:10.1111/j.1538-7836.2009.03520.x. PMID 19552682.  open access publication - free to read
  11. ^ Broad, AJ; Sutherland, SK; Coulter, AR (17 May 1979). "The Lethality in mice of dangerous Australian and other snake venoms". Toxicon 17 (6): 661–664. doi:10.1016/0041-0101(79)90245-9. PMID 524395. Retrieved 29 December 2013. 
  12. ^ Rosen, FS. (31 July 2003). "Edwin J. Cohn and the Development of Protein Chemisty". The New England Journal of Medicine 349 (5): 511–512. doi:10.1056/NEJM200307313490522. Retrieved 31 December 2013. 
  13. ^ a b c d Matejtschuk, P; P., Dash, C.H., and Gascoigne, E.W. (December 2000). "Production of human albumin solution: a continually developing colloid". British Journal of Anaesthesia 85 (6): 887–895. doi:10.1093/bja/85.6.887. PMID 11732525. Retrieved 31 December 2013. 
  14. ^ Brodniewicz-Proba, T (December 1991). "Human Plasma Fractionation and the Impact of New Technologies on the Use and Quality of Plasma-derived Products". Blood Reviews 5 (4): 245–257. doi:10.1016/0268-960x(91)90016-6. PMID 1782484. Retrieved 31 December 2013. 
  15. ^ Kini, R. Manjunatha (2007). "Evolution of Three-Finger Toxins - a Versatile Mini Protein Scaffold". Acta Chimica Slovenica 58 (4): 693–701.  open access publication - free to read
  16. ^ Juarez, P.; Comas, I.; Gonzalez-Candelas, F.; Calvete, J. J. (2008). "Evolution of Snake Venom Disintegrins by Positive Darwinian Selection". Molecular Biology and Evolution 25 (11): 2391–2407. doi:10.1093/molbev/msn179. PMID 18701431.  open access publication - free to read
  17. ^ Lynch, Vincent J. (January 2007). "Inventing an arsenal: Adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes". BMC Evolutionary Biology 7 (2). doi:10.1186/1471-2148-7-2. PMC 1783844. PMID 17233905.  open access publication - free to read
  18. ^ Fry, B. G.; wüSter, W.; Kini, R. M.; Brusic, V.; Khan, A.; Venkataraman, D.; Rooney, A. P. (2003). "Molecular evolution and phylogeny of elapid snake venom three-finger toxins". Journal of Molecular Evolution 57 (1): 110–129. doi:10.1007/s00239-003-2461-2. PMID 12962311.  Closed access
  19. ^ Savitzky, Alan H. (November 1980). "The Role of Venom Delivery Strategies in Snake Evolution". Evolution 34 (6): 1194–1204. JSTOR 2408300.  Closed access
  20. ^ Pahari, S.; Bickford, D.; Fry, B. G.; Kini, R. M. (2007). "Expression pattern of three-finger toxin and phospholipase A2 genes in the venom glands of two sea snakes, Lapemis curtus and Acalyptophis peronii: Comparison of evolution of these toxins in land snakes, sea kraits and sea snakes". BMC Evolutionary Biology 7: 175. doi:10.1186/1471-2148-7-175. PMC 2174459. PMID 17900344.  open access publication - free to read
  21. ^ Barlow, A.; Pook, C. E.; Harrison, R. A.; Wuster, W. (July 2009). "Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution". Proceedings of the Royal Society B: Biological Sciences 276 (1666): 2443–9. doi:10.1098/rspb.2009.0048. JSTOR 30244073. PMC 2690460. PMID 19364745.  open access publication - free to read
  22. ^ McCue, M. D. (October 2007). "Prey envenomation does not improve digestive performance in western diamondback rattlesnakes (Crotalus atrox)". Journal of Experimental Zoology Part A: Ecological Genetics and Physiology 307A (10): 568–577. doi:10.1002/jez.411. PMID 17671964.  Closed access
  23. ^ Martin, Charles James; Lamb, George (1907). "Snake-poison and Snake-bite". In Allbutt, T.C., Rolleston N.D. A System of Medicine. London: MacMillan. pp. 783–821. 
  24. ^ McCleary, R. J.; Kini, R. M. (2013). "Non-enzymatic proteins from snake venoms: A gold mine of pharmacological tools and drug leads". Toxicon 62: 56–74. doi:10.1016/j.toxicon.2012.09.008. PMID 23058997.  edit
  25. ^ Zouari-Kessentini, R; Srairi-Abid, N; Bazaa, A; El Ayeb, M; Luis, J; Marrakchi, N (2013). "Antitumoral potential of Tunisian snake venoms secreted phospholipases A2". BioMed Research International 2013: 391389. doi:10.1155/2013/391389. PMC 3581298. PMID 23509718.  edit
  26. ^ Vyas, V. K.; Brahmbhatt, K; Bhatt, H; Parmar, U; Patidar, R (2013). "Therapeutic potential of snake venom in cancer therapy: Current perspectives". Asian Pacific Journal of Tropical Biomedicine 3 (2): 156–62. doi:10.1016/S2221-1691(13)60042-8. PMC 3627178. PMID 23593597.  edit
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External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Snake toxin Provide feedback

A family of venomous neurotoxins and cytotoxins. Structure is small, disulfide-rich, nearly all beta sheet.

Literature references

  1. Dufton MJ; , J Mol Evol 1984;20:128-134.: Classification of elapid snake neurotoxins and cytotoxins according to chain length: evolutionary implications. PUBMED:6433031 EPMC:6433031

  2. Jonassen I, Collins JF, Higgins DG; , Protein Sci 1995;4:1587-1595.: Finding flexible patterns in unaligned protein sequences. PUBMED:8520485 EPMC:8520485


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003571

Snake toxins belong to a family of proteins [PUBMED:6433031] which groups short and long neurotoxins, cytotoxins and short toxins, as well as a other miscellaneous venom peptides. Most of these toxins act by binding to the nicotinic acetylcholine receptors in the postsynaptic membrane of skeletal muscles and prevent the binding of acetylcholine, thereby blocking the excitation of muscles.

Snake toxins are proteins that consist of sixty to seventy five amino acids. Among the invariant residues are eight cysteines all involved in disulphide bonds. The structure is small, disulphide-rich, nearly all beta sheet.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan uPAR_Ly6_toxin (CL0117), which has the following description:

This superfamily contains snake toxins as well as extracellular cysteine rich domains.

The clan contains the following 5 members:

Activin_recp BAMBI PLA2_inh Toxin_1 UPAR_LY6

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(48)
Full
(594)
Representative proteomes NCBI
(666)
Meta
(0)
RP15
(3)
RP35
(3)
RP55
(3)
RP75
(6)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(48)
Full
(594)
Representative proteomes NCBI
(666)
Meta
(0)
RP15
(3)
RP35
(3)
RP55
(3)
RP75
(6)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(48)
Full
(594)
Representative proteomes NCBI
(666)
Meta
(0)
RP15
(3)
RP35
(3)
RP55
(3)
RP75
(6)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Overington
Previous IDs: toxin; toxin_1;
Type: Domain
Author: Eddy SR
Number in seed: 48
Number in full: 594
Average length of the domain: 60.80 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 79.57 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.8
Noise cut-off 20.4 20.5
Model length: 63
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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The tree shows the occurrence of this domain across different species. More...

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Interactions

There are 2 interactions for this family. More...

Neur_chan_LBD Toxin_1

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Toxin_1 domain has been found. There are 141 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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