Crotamine | |||||||
---|---|---|---|---|---|---|---|
![]() | |||||||
Identifiers | |||||||
Organism | ? | ||||||
Symbol | CRO2 | ||||||
UniProt | Q9PWF3 | ||||||
|
Crotamine is a toxin present in the venom of the South American rattlesnake ( Crotalus durissus terrificus ). It is a 42-residue long protein containing 11 basic residues (9 lysines, 2 arginines) and 6 cysteines. It has also been isolated from the venom of North American prairie rattlesnake, Crotalus viridis viridis . It was first isolated and purified by Brazilian scientist José Moura Gonçalves, and later intensively studied by his group of collaborators at the Medical School of Ribeirão Preto of the University of São Paulo.
Crotamine has a number of biological actions: it acts on cell membrane's sodium channels, is slightly analgesic and is myotoxic, i.e., it penetrates the cells of muscles and promotes necrosis. [1] Crotamine is homologous with other venom myotoxins and is similar to α-,β-defensins.
The amino acid sequence (YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGSG, Cys4-Cys36, Cys11-Cys30, Cys18-Cys37) and the 3D molecular structure of crotamine have already been determined.
The protein structure of crotamine could not be initially determined through protein crystallization nor X-ray diffraction. [2] It was speculated that the difficulty was because crotamine has so many isoforms, leading to the formation of aggregates and different possible conformations of the protein. The structure and the shape of the protein was proposed through a 3D model generated by Siqueira et al. (2002) based on computational calculations that were supported with intensive molecular dynamics simulations and homology modeling procedures. Afterwards, Nicastro et al. (2003) discovered the structure of crotamine through nuclear magnetic resonance spectroscopy. Crotamine has a topology that was never before seen in active toxins that target ion channels; the protein is composed of a short N-terminal alpha helix, a type of protein formation, and a small antiparallel triple-stranded beta-sheet, another type of protein formation, arranged in an ab1b2b3 topology. Crotamine has similar structural fold conformations to the human b-defensin family as well as identical disulfide bridges arrangement. [2]
[Figure needed]
The gene and chromosome location responsible for its synthesis have been identified by the group led by Gandhi Rádis-Baptista, working at the Instituto Butantan, in São Paulo, Brazil. The mRNA has about 340 nucleotides and codifies a pre-crotamine, including the signal peptide, the mature crotamine, and a final lysine.
The Crotamine gene was the first gene to be mapped on a snake chromosome. [2] The gene responsible for coding the crotamine protein is labeled as Crt-p1 and its base pair sequence length is about 1.1kbp or 1100 bp. It was reported that the crotamine gene was isolated twice from two different specimens, one in a method that resulted in a gene size of 1.8 kbp and in the other specimen a gene size of 1.1 kbp. [3] The gene has been previously isolated in the C. durissus terrificus genome and the protein itself belongs to a group of small basic polypeptide myotoxins (SBPM). The contents of Crotalus venoms can vary according to subspecies and geographical location. [4] The Crt-p1 gene, as described by Radis-Bastista et al. 2003, consists of about three exons separated by one short phase-2 (140 bp) and one long phase-1 (900 bp) intron. Exon 1 codes for the first 19 amino acids of the signal peptide and includes the 5’-untranslated region. Exon 2 codes 39 amino acids to the mature crotamine and three signal peptide amino acids. Exon 3 codes for the terminal lysine and the last three amino acids of the mature toxin. Research on SBPM amino acid sequences among different Crotalus species has revealed a high degree of likeness ranging from 83% - 98%. [3]
The amino acid code of proteins in the small basic polypeptide myotoxin family, which includes crotamine, have been sequenced. They were found to be similar with an average of 83% divergence. A crotamine amino acid sequence was compared to that of cloned DNA of myotoxin a, (the myotoxin used to model how SBPMs work). In the comparison, exon coding regions including the mature myotoxin and the signal peptide were 98% and 100% similar, respectively. The untranslated regions for 5’ and 3’ between the sample and the myotoxin a cDNA was 60% and 80%, respectively. When comparing the amino acid sequences of other proteins not in the SBPM family found in snake venoms, there is usually large divergence. When looking at the SBPM proteins, they have high similarity between different subspecies of the Crotalus genus and between different individuals of the same subspecies. This indicates, according to the Radis-Batista et al. 2003 study, that the crotamine gene and other SBPM genes have evolved recently.
Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved venom apparatus, such as fangs or a stinger, in a process called envenomation. Venom is often distinguished from poison, which is a toxin that is passively delivered by being ingested, inhaled, or absorbed through the skin, and toxungen, which is actively transferred to the external surface of another animal via a physical delivery mechanism.
Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is injected by unique fangs during a bite, whereas some species are also able to spit venom.
Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.
Convulxin is a snake venom toxin found in a tropical rattlesnake known as Crotalus durissus terrificus. It belongs to the family of hemotoxins, which destroy red blood cells or, as is the case with convulxin, induce blood coagulation.
Myotoxins are small, basic peptides found in snake venoms and lizard venoms. This involves a non-enzymatic mechanism that leads to severe muscle necrosis. These peptides act very quickly, causing instantaneous paralysis to prevent prey from escaping and eventually death due to diaphragmatic paralysis.
Calciseptine (CaS) is a natural neurotoxin isolated from the black mamba Dendroaspis p. polylepis venom. This toxin consists of 60 amino acids with four disulfide bonds. Calciseptine specifically blocks L-type calcium channels, but not other voltage-dependent Ca2+ channels such as N-type and T-type channels.
Crotalus durissus, known as the South American rattlesnake, tropical rattlesnake, and by other names, is a highly venomous pit viper species found in South America. It is the most widely distributed member of its genus. Currently, seven subspecies are recognized.
In enzymology, an L-amino acid oxidase (LAAO) (EC 1.4.3.2) is an enzyme that catalyzes the chemical reaction.
BmKAEP is a neurotoxin from the venom of the Manchurian scorpion (Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.
Atrolysin A is an enzyme that is one of six hemorrhagic toxins found in the venom of western diamondback rattlesnake. This endopeptidase has a length of 419 amino acid residues. The metalloproteinase disintegrin-like domain and the cysteine-rich domain of the enzyme are responsible for the enzyme's hemorrhagic effects on organisms via inhibition of platelet aggregation.
Atrolysin C is an enzyme. This enzyme catalyses the following chemical reaction
CSTX is a name given to a group of closely related neurotoxic peptides present in the venom of the wandering spider Cupiennius salei. There are twenty types so far described for this protein group. However, some are reclassified into cupiennins group of toxin, including CSTX-3, -4, -5, and -6, because of their chemical affinity. The first thirteen were isolated and identified in 1994 by Lucia Kuhn-Nentwig, Johann Schaller, and Wolfgang Nentwig of the Zoological Institute at the University of Bern, Switzerland. The different types are most likely the products of splicing variant of the same gene. They are all L-type calcium channel blockers, and also exhibit cytolytic activity by forming an alpha-helix across the cell membrane in mammalian neurons. They also inhibit voltage-gated calcium channels in insect neurons.
Cupiennins are a group of small cytolytic peptides from the venom of the wandering spider Cupiennius salei. They are known to have high bactericidal, insecticidal and haemolytic activities. They are chemically cationic α-helical peptides. They were isolated and identified in 2002 as a family of peptides called cupiennin 1. The sequence was determined by a process called Edman degradation, and the family consists of cupiennin 1a, cupiennin 1b, cupiennin 1c, and cupiennin 1d. The amino acid sequences of cupiennin 1b, c, and d were obtained by a combination of sequence analysis and mass spectrometric measurements of comparative tryptic peptide mapping. Even though they are not strong toxins, they do enhance the effect of the spider venom by synergistically enhancing other components of the venom, such CSTX.
Heteroscopine (HS-1) is the main component of the venom of Heterometrus laoticus. It belongs to the Scorpine toxin family. It is a polypeptide consisting of a defensin-like component on its N-terminal end and a putative potassium channel blocking component on its C-terminal end. It has antimicrobial effect on some bacteria, but not on fungi.
Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.
Venom in snakes and some lizards is a form of saliva that has been modified into venom over its evolutionary history. In snakes, venom has evolved to kill or subdue prey, as well as to perform other diet-related functions. While snakes occasionally use their venom in self defense, this is not believed to have had a strong effect on venom evolution. The evolution of venom is thought to be responsible for the enormous expansion of snakes across the globe.
Kaliseptine (AsKS) is a neurotoxin which can be found in the snakelocks anemone Anemonia viridis. It belongs to a class of sea anemone neurotoxins that inhibits voltage-gated potassium channels.
Three-finger proteins or three-finger protein domains are a protein superfamily consisting of small, roughly 60-80 amino acid residue protein domains with a common tertiary structure: three beta strand loops extended from a hydrophobic core stabilized by disulfide bonds. The family is named for the outstretched "fingers" of the three loops. Members of the family have no enzymatic activity, but are capable of forming protein-protein interactions with high specificity and affinity. The founding members of the family, also the best characterized by structure, are the three-finger toxins found in snake venom, which have a variety of pharmacological effects, most typically by disruption of cholinergic signaling. The family is also represented in non-toxic proteins, which have a wide taxonomic distribution; 3FP domains occur in the extracellular domains of some cell-surface receptors as well as in GPI-anchored and secreted globular proteins, usually involved in signaling.
Crotoxin (CTX) is the main toxic compound in the snake venom of the South American rattlesnake, Crotalus durissus terrificus. Crotoxin is a heterodimeric beta-neurotoxin, composed of an acidic, non-toxic and non-enzymatic subunit (CA), and a basic, weakly toxic, phospholipase A2 protein (CB). This neurotoxin causes paralysis by both pre- and postsynaptic blocking of acetylcholine signalling.
U7-ctenitoxin-Pn1a (or U7-CNTX-Pn1a for short) is a neurotoxin that blocks TRPV1 channels, and can exhibit analgestic effects. It is naturally found in the venom of Phoneutria nigriventer.