Cll2
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Cll2
Beta-toxin Cll2, shortened to Cll2, is a toxin in the venom of the Mexican Scorpion species '' Centruroides limpidus limpidus''. The toxin belongs to the β-class family of sodium channel-inhibiting scorpion toxins. It affects voltage-dependent activation, conductance and resurgent currents of voltage gated sodium channels by binding to site 4. Etymology and Source Cll2 is named after the venom produced by the species ''Centruroides limpidus limpidus'' (Cll, a Mexican scorpion). Cll1 and Cll2 are both derived from this venom. The ''Centruroides limpidus limpidus'' species is a member of the only genus that represents a life hazard to humans in Mexico, and is mainly found in the state of Morelos. Chemistry Cll2 belongs to the beta-type of sodium channel-inhibiting scorpion toxins. The Cll venom consists of six fractions, of which only Cll2 is lethal, amounting to ~42% of the venom. Cll2 consists of thirteen sub-fractions, of which sub-fraction 9 is the largest. The molecular we ...
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Centruroides
''Centruroides'' is a genus of scorpions of the family Buthidae. Several North American species are known by the common vernacular name bark scorpion. Numerous species are extensively found throughout the southern United States, Mexico, Central America, the Antilles and northern South America. Some are known for their interesting patterning or large size (among Buthidae); most if not all fluoresce strongly under ultraviolet illumination, except after moulting. They contain several highly venomous species, and fatalities are known to occur. The venom of the Mexican scorpion ''Centruroides limpidus limpidus'' contains the neurotoxins Cll1 and Cll2. Taxonomy The number of species accepted as valid may vary, depending on the authority. The genus is highly speciose, containing at least 100 species: * ''Centruroides alayoni'' Armas, 1999 * ''Centruroides altagraciae'' Teruel, de Armas & Kovarik, 2015 * ''Centruroides anchorellus'' Armas, 1976 * ''Centruroides arctimanus'' Armas, 19 ...
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Scorpion Toxin
Scorpion toxins are proteins found in the venom of scorpions. Their toxic effect may be mammal- or insect-specific and acts by binding with varying degrees of specificity to members of the Voltage-gated ion channel superfamily; specifically, voltage-gated sodium channels, voltage-gated potassium channels, and Transient Receptor Potential (TRP) channels. The result of this action is to activate or inhibit the action of these channels in the nervous and cardiac organ systems. For instance, α-scorpion toxins MeuNaTxα-12 and MeuNaTxα-13 from ''Mesobuthus eupeus'' are neurotoxins that target voltage-gated Na+ channels (Navs), inhibiting fast inactivation. ''In vivo'' assays of MeuNaTxα-12 and MeuNaTxα-13 effects on mammalian and insect Navs show differential potency. These recombinants (MeuNaTxα-12 and MeuNaTxα-13) exhibit their preferential affinity for mammalian and insect Na+ channels at the α-like toxins' active site, site 3, in order to inactivate the cell membrane depolari ...
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Cll1
Toxin Cll1 is a toxin from the venom of the Mexican scorpion '' Centruroides limpidus limpidus'', which changes the activation threshold of sodium channels by binding to neurotoxin binding site 4, resulting in increased excitability. Etymology and source The toxin Cll1 is named after its producing species, '' Centruroides limpidus limpidus''. Along with Cll1, multiple toxins are excreted in its venom. Chemistry Cll1 is a long chain neuropeptide belonging to the scorpion toxin superfamily. Cll1 is classified as a member of the beta-toxin subfamily. The global secondary structure of Cll1 is similar to that of other scorpion beta-toxins, including the alpha-helix, triple stranded antiparallel beta-sheet, and the four disulfide bridges. The higher affinity for crustacean rather than mammalian sodium channels has been attributed to the presence of Trp18, a hydrophobic amino acid at the surface of Cll1. Target Cll1 targets, like the classical scorpion beta-toxin, the voltag ...
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Morelos
Morelos (), officially the Free and Sovereign State of Morelos ( es, Estado Libre y Soberano de Morelos), is one of the 32 states which comprise the Federal Entities of Mexico. It is divided into 36 municipalities and its capital city is Cuernavaca. Morelos is a landlocked state located in South Central Mexico. It is bordered by Mexico City to the north, and by the states of México to the northeast and northwest, Puebla to the east and Guerrero to the southwest. Morelos is the second-smallest state in the nation, just after Tlaxcala. It was part of a very large province, the State of Mexico, until 1869 when Benito Juárez decreed that its territory would be separated and named in honor of José María Morelos y Pavón, who defended the city of Cuautla from royalist forces during the Mexican War of Independence. Most of the state enjoys a warm climate year-round, which is good for the raising of sugar cane and other crops. Morelos has attracted visitors from the Valley of ...
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Voltage-gated Sodium Channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change ("voltage-gated", "voltage-sensitive", or "voltage-dependent" sodium channel; also called "VGSCs" or "Nav channel") or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through three different states called resting, active and inactive states. Even though the resting and inactive states would not allow the ions to flow through the channels the difference exists with respect to their structural conformation. Selectivity Sodium channels are highly selective for the transport of ions across cell membr ...
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SCN8A
Sodium channel protein type 8 subunit alpha also known as Nav1.6 is a membrane protein encoded by the ''SCN8A'' gene. Nav1.6 is one sodium channel isoform and is the primary voltage-gated sodium channel at each node of Ranvier. The channels are highly concentrated in sensory and motor axons in the peripheral nervous system and cluster at the nodes in the central nervous system. Structure Nav1.6 is encoded by the SCN8A gene which contains 27 exons and measures 170 kb. The voltage gated sodium channel is composed of 1980 residues. Like other sodium channels, Nav1.6 is a monomer composed of four homologous domains (I-IV) and 25 transmembrane segments. SCN8A encodes S3-S4 transmembrane segments which form an intracellular loop. Function Like other sodium ion channels, Nav1.6 facilitates action potential propagation when the membrane potential is depolarized by an influx of Na+ ions. However, Nav1.6 is able to sustain repetitive excitation and firing. The high frequency firing ch ...
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LD50
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity. The test was created by J.W. Trevan in 1927. The term semilethal dose is occasionally used in the same sense, in particular with translations of foreign language text, but can also refer to a sublethal dose. LD50 is usually determined by tests on animals such as laboratory mice. In 2011, the U.S. Food and Drug Administration approved alternative methods to LD50 for testing the cosmetic drug Botox without animal tests. Conventions The LD50 is usually expressed as the mass of substance administered per unit ...
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Neurotoxins
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nervous tissue.Olney 2002 The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), glutamate,Choi 1987 nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin,Simpson 1986 and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or c ...
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Scorpion Toxins
Scorpions are predatory arachnids of the order Scorpiones. They have eight legs, and are easily recognized by a pair of grasping pincers and a narrow, segmented tail, often carried in a characteristic forward curve over the back and always ending with a stinger. The evolutionary history of scorpions goes back 435 million years. They mainly live in deserts but have adapted to a wide range of environmental conditions, and can be found on all continents except Antarctica. There are over 2,500 described species, with 22 extant (living) families recognized to date. Their taxonomy is being revised to account for 21st-century genomic studies. Scorpions primarily prey on insects and other invertebrates, but some species hunt vertebrates. They use their pincers to restrain and kill prey, or to prevent their own predation. The venomous sting is used for offense and defense. During courtship, the male and female grasp each other's pincers and dance while he tries to move her onto his sp ...
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