Cll1
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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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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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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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Chemical Structure Cll1
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., without breaking chemical bonds. Chemical substances can be simple substances (substances consisting of a single chemical element), chemical compounds, or alloys. Chemical substances are often called 'pure' to set them apart from mixtures. A common example of a chemical substance is pure water; it has the same properties and the same ratio of hydrogen to oxygen whether it is isolated from a river or made in a laboratory. Other chemical substances commonly encountered in pure form are diamond (carbon), gold, table salt ( sodium chloride) and refined sugar ( sucrose). However, in practice, no substance is entirely pure, and chemical purity is specified according to the intended use of the chemical. Chemical substances exist as solids, liqu ...
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Alpha Helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earlier along the protein sequence. The alpha helix is also called a classic Pauling–Corey–Branson α-helix. The name 3.613-helix is also used for this type of helix, denoting the average number of residues per helical turn, with 13 atoms being involved in the ring formed by the hydrogen bond. Among types of local structure in proteins, the α-helix is the most extreme and the most predictable from sequence, as well as the most prevalent. Discovery In the early 1930s, William Astbury showed that there were drastic changes in the X-ray fiber diffraction of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a coiled molecular structure with a characteristic repeat of ≈. Astb ...
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Beta Sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, notably Alzheimer's disease. History The first β-sheet structure was proposed by William Astbury in the 1930s. He proposed the idea of hydrogen bonding between the peptide bonds of parallel or antiparallel extended β-strands. However, Astbury did not have the necessary data on the bond geometry of the amino acids in order to build accurate models, especially since he did not then know that the peptide bond was planar. A refined versi ...
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Disulfide
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In biology, disulfide bridges formed between thiol groups in two cysteine residues are an important component of the secondary and tertiary structure of proteins. ''Persulfide'' usually refers to compounds. In inorganic chemistry disulfide usually refers to the corresponding anion (−S−S−). Organic disulfides Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organo sulfur chemistry are symmetrical disulfides. Unsymmetrical disulfides (also called heterodisulfides) are compounds of the formula . They are less common in organic chemistry, but most disulfides in nature are unsymmetrical. Properties The disulfide bonds are strong, with a typical bond dissociation energy of 60 kcal/mol (251&nbs ...
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Tryptophan
Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. It is essential in humans, meaning that the body cannot synthesize it and it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3. It is encoded by the codon UGG. Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–; pKa = 9.39) and the carboxylic acid is deprotonated ( –COO−; pKa = 2.38). Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. Function Amino acids, including tryptophan, are used as building blocks in protein biosynthesis, and proteins are required to sustain life. Man ...
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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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Median Lethal Dose
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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Bouvardia Ternifolia
''Bouvardia ternifolia'', the firecracker bush, is a shrub widespread across much of Mexico, the range extending south into Honduras and north into the southwestern United States (Arizona, New Mexico and Texas Texas (, ; Spanish: ''Texas'', ''Tejas'') is a state in the South Central region of the United States. At 268,596 square miles (695,662 km2), and with more than 29.1 million residents in 2020, it is the second-largest U.S. state by ...). ''Bouvardia ternifolia'' is a shrub up to 120 cm (4 feet) tall. It has dark green, narrowly egg-shaped leaves. Flowers are speculacular: long, tubular, bright scarlet, up to 10 cm (2 inches) long, in clusters at the ends of the branches. Hummingbirds frequently imbibe the nectar from the blooms. ''Bouvardia ternifolia'' is widely cultivated as an ornamental because of its showy flowers.Schlechtendal, Diederich Franz Leonhard von, in Planchon, Jules Émile. 1855. Flore des Serres et des Jardins de l'Europe 10: ...
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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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