Protoxin-II
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Protoxin-II
Protoxin-II, also known as ProTx-II, PT-II or β/ω-TRTX-Tp2a, is a neurotoxin that inhibits certain voltage-gated calcium and voltage-gated sodium channels. This toxin is a 30-residue disulfide-rich peptide that has unusually high affinity and selectivity toward the human Nav1.7. channel. Sources Protoxin-II is a neurotoxin that is derived from the venom of the Peruvian green velvet tarantula (''Thrixopelma pruriens ''Thrixopelma pruriens'', known as the Peruvian green velvet tarantula, is a species of tarantula found in Chile and Perú in South America. Though docile, this species is rarely kept as a pet in part due to its tendency to fling urticating ha ...''). Chemistry ProTx-II is a 30-amino acid peptide with a molecular weight of 3826.65 Da. The structure of ProTx-II is amphipathic, with mostly hydrophobic residues on one face of the toxin. The toxin is formed by an inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region. Target ProTx-II ...
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Neurotoxin
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 com ...
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Amphipathic
An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compound is called amphiphilic or amphipathic. Common amphiphilic substances are soaps, detergents, and lipoproteins. The phospholipid amphiphiles are the major structural component of cell membranes. Amphiphiles are the basis for a number of areas of research in chemistry and biochemistry, notably that of lipid polymorphism. Organic compounds containing hydrophilic groups at both ends of the molecule are called bolaamphiphile, bolaamphiphilic. The micelles they form in the aggregate are prolate. Structure The lipophilic group is typically a large hydrocarbon Moiety (chemistry), moiety, such as a long chain of the form CH3(CH2)n, with n > 4. The hydrophilic group falls into one of the following categories: # charged groups #* anionic. Examples ...
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Ion Channel Toxins
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convention. The net charge of an ion is not zero because its total number of electrons is unequal to its total number of protons. A cation is a positively charged ion with fewer electrons than protons while an anion is a negatively charged ion with more electrons than protons. Opposite electric charges are pulled towards one another by electrostatic force, so cations and anions attract each other and readily form ionic compounds. Ions consisting of only a single atom are termed atomic or monatomic ions, while two or more atoms form molecular ions or polyatomic ions. In the case of physical ionization in a fluid (gas or liquid), "ion pairs" are created by spontaneous molecule collisions, where each generated pair consists of a free electron and a ...
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Nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response. In nociception, intense chemical (e.g., capsaicin present in Chili pepper or Cayenne pepper), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory neurons called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or perception, of pain in sentient beings. Detection of noxious stimuli Potentially damaging mechanical, thermal, and chemical stimuli are detected ...
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Sensory Neurons
Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal ganglia of the spinal cord. The sensory information travels on the afferent nerve fibers in a sensory nerve, to the brain via the spinal cord. The stimulus can come from ''exteroreceptors'' outside the body, for example those that detect light and sound, or from ''interoreceptors'' inside the body, for example those that are responsive to blood pressure or the sense of body position. Types and function Different types of sensory neurons have different sensory receptors that respond to different kinds of stimuli. There are at least six external and two internal sensory receptors: External receptors External receptors that respond to stimuli from outside the body are called ex ...
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Free Nerve Endings
A free nerve ending (FNE) or bare nerve ending, is an unspecialized, afferent nerve fiber sending its signal to a sensory neuron. ''Afferent'' in this case means bringing information from the body's periphery toward the brain. They function as cutaneous nociceptors and are essentially used by vertebrates to detect noxious stimuli that often result in pain. Structure Free nerve endings are unencapsulated and have no complex sensory structures. They are the most common type of nerve ending, and are most frequently found in the skin. They penetrate the dermis and end in the stratum granulosum. FNEs infiltrate the middle layers of the dermis and surround hair follicles. Types Free nerve endings have different rates of adaptation, stimulus modalities, and fiber types. Rate of adaptation Different types of FNE can be rapidly adapting, intermediate adapting, or slowly adapting. A delta type II fibers are fast-adapting while A delta type I and C fibers are slowly adapting.Rolf-Detlef T ...
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IC50
The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, ''in vitro'', a given biological process or biological component by 50%. The biological component could be an enzyme, cell, cell receptor or microorganism. IC50 values are typically expressed as molar concentration. IC50 is commonly used as a measure of antagonist drug potency in pharmacological research. IC50 is comparable to other measures of potency, such as EC50 for excitatory drugs. EC50 represents the dose or plasma concentration required for obtaining 50% of a maximum effect ''in vivo''. IC50 can be determined with functional assays or with competition binding assays. Sometimes, IC50 values are converted to the pIC50 scale. :\ce = -\log_ \ce Due to the minus sign, higher values of pIC50 indica ...
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Inhibitor Cystine Knot
An inhibitor cystine knot (aka ICK or Knottin) is a protein structural motif containing three disulfide bridges. Knottins are one of three folds in the cystine knot motif; the other closely related knots are the Growth Factor Cystine Knot (GFCK) and the Cyclic Cystine Knot (CCK; cyclotide). Types include a) cyclic mobius, b) cyclic bracelet, c) acyclic inhibitor knottins. Cystine knot motifs are found frequently in nature in a plethora of plants, animals, and fungi and serve diverse functions from appetite suppression to anti-fungal activity. Along with the sections of polypeptide between them, two disulfides form a loop through which the third disulfide bond (linking the 3rd and 6th cysteine in the sequence) passes, forming a knot. The motif is common in invertebrate toxins such as those from arachnids and molluscs. The motif is also found in some inhibitor proteins found in plants, but the plant and animal motifs are thought to be a product of convergent evolution. The ICK moti ...
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Thrixopelma Pruriens
''Thrixopelma pruriens'', known as the Peruvian green velvet tarantula, is a species of tarantula found in Chile and Perú in South America. Though docile, this species is rarely kept as a pet in part due to its tendency to fling urticating hairs with minimal provocation. In 2014, researchers at Yale University Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wo ... identified a toxin called Protoxin-I from the tarantula's venom that shows promise as a new painkiller drug. The toxin reduces activity in an ion channel associated with inflammation and neuropathic pain, making it potentially suitable as a treatment for both normal pain and pathological pain syndromes. References Theraphosidae Spiders of South America Spiders described in 1998 {{Theraphosidae-stub ...
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Voltage-gated Calcium Channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VGCCs are normally closed. They are activated (''i.e.'': opened) at depolarized membrane potentials and this is the source of the "voltage-gated" epithet. The concentration of calcium (Ca2+ ions) is normally several thousand times higher outside the cell than inside. Activation of particular VGCCs allows a Ca2+ influx into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, exc ...
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Peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A polypeptide is a longer, continuous, unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological polymers and oligomers, alongside nucleic acids, oligosaccharides, polysaccharides, and others. A polypeptide that contains more than approximately 50 amino acids is known as a protein. Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule such as DNA or RNA, or to complex macromolecular assemblies. Amino acids that have been incorporated into peptides are termed residues. A water molecule is released during formation of each amide bond.. All peptides except cyclic pep ...
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