Latisemin is a cysteine-rich secretory protein that can be isolated from the venom of the Black-banded sea krait, a sea snake indigenous to the warmer waters of the western Pacific Ocean. It is a toxin that inhibits cyclic nucleotide-gated ion channels [1] and blocks L-type calcium channels, thereby reducing smooth muscle contraction. [2]
Latisemin is a component of the venom produced by the Erabu sea snake ( Laticauda semifasciata ) of the family Elapidae and the Laticauda genus. These sea snakes inhabit coral reef areas in the seas of Southern Japan, Southeast Asia, and Australia. [2] Though highly venomous, this snake is comparatively unaggressive, and is in fact caught and eaten in Erabu soup in Japan.
Latisemin has a molecular weight of 24 kDa and consists of 217 amino acids. [1] [3] It belongs to the CRISP (cysteine-rich secretory protein) glycoprotein subfamily, [4] which are single chain polypeptides containing strictly conserved cysteines [1] (cysteines not oxidised to cystine and thus not providing disulfide bond support to tertiary protein structure). They are secretory proteins, meaning they are secreted from cells into extracellular fluid.
Latisemin strongly blocks depolarization- (but not caffeine-) induced smooth muscle contraction, [2] suggesting that it blocks L-type calcium channels. Its mode of action is similar to that of some other snake venom toxins from the CRISP family, like ablomin from the Japanese Mamushi snake and triflin from the Habu snake. [2] They also inhibit cyclic nucleotide-gated ion channels. [1]
Other snake venom proteins in the CRISP family:
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.
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.
Ophanin is a toxin found in the venom of the King Cobra, which lives throughout South East Asia. This toxin belongs to the cysteine-rich secretory protein (CRISP) family. Ophanin weakly blocks the contraction of smooth muscles elicited by high potassium-induced depolarization, suggesting that it inhibits voltage-dependent calcium channels.
Gloydius blomhoffii, commonly known as the mamushi, Japanese moccasin, Japanese pit viper, Qichun snake, Salmusa or Japanese mamushi, is a venomous pit viper species found in Japan. It was once considered to have 4 subspecies, but it is now considered monotypic.
Taicatoxin (TCX) is a snake toxin that blocks voltage-dependent L-type calcium channels and small conductance Ca2+-activated K+ channels. The name taicatoxin (TAIpan + CAlcium + TOXIN) is derived from its natural source, the taipan snake, the site of its action, calcium channels, and from its function as a toxin. Taicatoxin was isolated from the venom of Australian taipan snake, Oxyuranus scutellatus scutellatus. TCX is a secreted protein, produced in the venom gland of the snake.
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.
Crotamine is a toxin present in the venom of the South American rattlesnake. It is a 42-residue long protein containing 11 basic residues 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.
Cysteine-rich secretory protein 3 is a cysteine-rich secretory protein that in humans is encoded by the CRISP3 gene.
BmTx3 is a neurotoxin, which is a component of the venom of the scorpion Buthus Martensi Karsch. It blocks A-type potassium channels in the central nervous system and hERG-channels in the heart.
Ablomin is a toxin present in the venom of the Japanese Mamushi snake, which blocks L-type voltage-gated calcium channels.
Triflin is a cysteine-rich secretory protein (CRISP), which is excreted by the venom gland of the Habu snake. Triflin reduces high potassium-induced smooth muscle contraction, suggesting a blocking effect on L-type calcium channels.
Piscivorin is a component of snake venom secreted by the Eastern Cottonmouth. It is a member of the cysteine-rich secretory protein (CRISP) family, which blocks voltage-dependent calcium channels.
Cysteine-rich secretory proteins, often abbreviated as CRISPs, are a group of glycoproteins. They are a subgroup of the CRISP, antigen 5 and Pr-1 (CAP) protein superfamily and also contain a domain related to the ShK toxins. They are substantially implicated in the functioning of the mammalian reproductive system. CRISPs are also found in a variety of snake venoms where they inhibit both smooth muscle contraction and cyclic nucleotide-gated ion channels.
The CAP superfamily is a large superfamily of secreted proteins that are produced by a wide range of organisms, including prokaryotes and non-vertebrate eukaryotes.
Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation. From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome. The trial was halted in March 2012 due to inadequate efficacy. The selective sPLA2 inhibitor varespladib (IC50 value 0.009 μM in chromogenic assay, mole fraction 7.3X10-6) was studied in the VISTA-16 randomized clinical trial (clinicaltrials.gov Identifier: NCT01130246) and the results were published in 2014. The sPLA2 inhibition by varespladib in this setting seemed to be potentially harmful, and thus not a useful strategy for reducing adverse cardiovascular outcomes from acute coronary syndrome. Since 2016, scientific research has focused on the use of Varespladib as an inhibitor of snake venom toxins using various types of in vitro and in vivo models. Varespladib showed a significant inhibitory effect to snake venom PLA2 which makes it a potential first-line drug candidate in snakebite envenomation therapy. In 2019, the U.S. Food and Drug Administration (FDA) granted varespladib orphan drug status for its potential to treat snakebite.
α-Neurotoxins are a group of neurotoxic peptides found in the venom of snakes in the families Elapidae and Hydrophiidae. They can cause paralysis, respiratory failure, and death. Members of the three-finger toxin protein family, they are antagonists of post-synaptic nicotinic acetylcholine receptors (nAChRs) in the neuromuscular synapse that bind competitively and irreversibly, preventing synaptic acetylcholine (ACh) from opening the ion channel. Over 100 α-neurotoxins have been identified and sequenced.
Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.
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.
Pi4 is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels.
Three-finger toxins are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic proteins that share a similar protein fold. The group is named for its common structure consisting of three beta strand loops connected to a central core containing four conserved disulfide bonds. The 3FP protein domain has no enzymatic activity and is typically between 60-74 amino acid residues long. Despite their conserved structure, three-finger toxin proteins have a wide range of pharmacological effects. Most members of the family are neurotoxins that act on cholinergic intercellular signaling; the alpha-neurotoxin family interacts with muscle nicotinic acetylcholine receptors (nAChRs), the kappa-bungarotoxin family with neuronal nAChRs, and muscarinic toxins with muscarinic acetylcholine receptors (mAChRs).