Ctri9577
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Ctri9577
Ctri9577 (α-KTx15.10) is a neurotoxin present in the venom of the ''Chaerilus tricostatus'' scorpion, which is a potent blocker of the voltage-gated potassium channel Kv1.3, and a gating modifier of Kv4.3 channels. * Etymology and Source The Ctri9577 toxin is a component of the venom of the scorpion ''Chaerilus tricostatus''. The name of the toxin derives from the first letter of the genus of ''Chaerilus'' (C), species (tri), and the clone number in the cDNA library (9577). Chemistry Ctri9577 is a member of the α-KTx15 subfamily, which specifically target potassium channels. The mature peptide of Ctri9577, which is the peptide without the signal sequence, consists of 39 amino acids (4.44 kDa), including six cysteines which form three disulfide bridges (see table 1). Other scorpion toxins specific for K+ channels (KTx) commonly form a CSα/β (cysteine-stabilized α-helix-β-sheet) fold.
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Chaerilus
''Chaerilus'' is a genus of scorpions in the family Chaerilidae. They live in tropical parts of South Asia and Southeast Asia. A fossil genus '' Electrochaerilus'' is known from the Late Cretaceous (Cenomanian) aged Burmese amber. Description Total length is 15 to 75.4 mm. Species It contains the following species: *'' Chaerilus agilis'' Pocock, 1899 *'' Chaerilus andamanensis'' Lourenço, Duhem & Leguin, 2011 *'' Chaerilus annapurna'' Lourenço & Duhem, 2010 *'' Chaerilus anneae'' Lourenço, 2012 *'' Chaerilus assamensis'' Kraepelin, 1913 *'' Chaerilus borneensis'' Simon, 1880 *''Chaerilus cavernicola'' Pocock, 1894 *'' Chaerilus celebensis'' Pocock, 1894 *'' Chaerilus ceylonensis'' Pocock, 1894 *'' Chaerilus chapmani'' Vachon & Lourenço, 1985 *'' Chaerilus cimrmani'' Kovařík, 2012 *''Chaerilus conchiformus'' Zhu, Han & Lourenço, 2008 *''Chaerilus dibangvalleycus'' Bastawade, 2006 *''Chaerilus granulatus'' Kovarík, Lowe, Hoferek, Forman & Král, 2015 *''Chaerilus hof ...
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Neurotoxin
Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), 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 ...
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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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Action Potential
An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of Membrane potential#Cell excitability, excitable cells, which include animal cells like neurons and myocyte, muscle cells, as well as some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells. In neurons, action potentials play a central role in cell–cell interaction, cell–cell communication by providing for—or with regard to saltatory conduction, assisting—the propagation of signals along the neuron's axon toward axon terminal, synaptic boutons situated at the ends of an axon; these signals can then connect wit ...
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Gating (electrophysiology)
In electrophysiology, the term gating refers to the opening (activation) or closing (by deactivation or inactivation) of ion channels. This change in conformation is a response to changes in transmembrane voltage. When ion channels are in a 'closed' (non-conducting) state, they are impermeable to ions and do not conduct electrical current. When ion channels are in their open state, they conduct electrical current by allowing specific types of ions to pass through them, and thus, across the plasma membrane of the cell. Gating is the process by which an ion channel transitions between its open and closed states. A variety of cellular changes can trigger gating, depending on the ion channel, including changes in voltage across the cell membrane (voltage-gated ion channels), chemicals interacting with the ion channel (ligand-gated ion channels), changes in temperature, stretching or deformation of the cell membrane, addition of a phosphate group to the ion channel (phosphorylation), ...
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IC50
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 microbe. 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 indicate ex ...
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Voltage-gated Potassium Channels
Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state. Classification Alpha subunits Alpha subunits form the actual conductance pore. Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels are grouped into 12 classes. These are labeled Kvα1-12. The following is a list of the 40 known human voltage-gated potassium channel alpha subunits grouped first according to function and then subgrouped according to the Kv sequence homology classification scheme: Delayed rectifier slowly inactivating or non-inactivating *Kvα1.x - Shaker-related: Kv1.1 ( KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.5 ( KCNA5), Kv1.6 ( KCNA6), Kv1.7 ( KCNA7), Kv1.8 ( KCNA10) *Kvα2.x - Shab-related: Kv2.1 ( KCNB1), Kv2.2 ( KCNB2) *Kv� ...
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Phylogenetic Tree
A phylogenetic tree or phylogeny is a graphical representation which shows the evolutionary history between a set of species or taxa during a specific time.Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA. In other words, it is a branching diagram or a tree showing the evolutionary relationships among various biological species or other entities based upon similarities and differences in their physical or genetic characteristics. In evolutionary biology, all life on Earth is theoretically part of a single phylogenetic tree, indicating common ancestry. Phylogenetics is the study of phylogenetic trees. The main challenge is to find a phylogenetic tree representing optimal evolutionary ancestry between a set of species or taxa. Computational phylogenetics (also phylogeny inference) focuses on the algorithms involved in finding optimal phylogenetic tree in the phylogenetic landscape. Phylogenetic trees may be rooted or unrooted. In a ''rooted'' p ...
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Protein Secondary Structure
Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary structure elements typically spontaneously form as an intermediate before the protein folds into its three dimensional tertiary structure. Secondary structure is formally defined by the pattern of hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone. Secondary structure may alternatively be defined based on the regular pattern of backbone dihedral angles in a particular region of the Ramachandran plot regardless of whether it has the correct hydrogen bonds. The concept of secondary structure was first introduced by Kaj Ulrik Linderstrøm-Lang at Stanford in 1952. Other types of biopolymers such as nucleic acids also possess characteristic secondary structures. Types ...
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Disulfide
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorganic chemistry, the anion appears in a few rare minerals, but the functional group has tremendous importance in biochemistry. Disulfide bridges formed between thiol groups in two cysteine residues are an important component of the tertiary and quaternary structure of proteins. Compounds of the form are usually called ''persulfides'' instead. Organic disulfides Structure Disulfides have a C–S–S–C dihedral angle approaching 90°. The S–S bond length is 2.03 Å in diphenyl disulfide, similar to that in elemental sulfur. Disulfides are usually symmetric but they can also be unsymmetric. Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organosulfur chemistry are symmetrical disulfides. Unsymme ...
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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, Alzheimer's disease and other proteinopathies. 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. ...
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Potassium Channel
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Function Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K+ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius). Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such as neurons, the delayed counterflow of potassium ions shapes the action potential. By contributing to the regulation of the cardiac action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone. They also regu ...
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