BmKTX
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BmKTX
BmKTX (alpha-KTx 3.6) is a scorpion neurotoxin which blocks the voltage gated potassium channel Kv1.3. Etymology and source The name BmK part of the toxin is derived from the name of the scorpion, ''Buthus martensi'' (Karsch). KTX also stands for the Kaliotoxin family, which this toxin is a part of. BmKTX is one of the toxins present in the venom of scorpion, found in mostly Mongolia, Korea and China. Chemistry Homology BmKTX belongs to the α-KTX family, more specifically, the α-KTX subfamily 3, both in terms of primary and 3D structure. The venom of this scorpion has led to the discovery of 77 different peptides, mainly related to ion channel toxins. Out of these toxins there are 14 short chain toxins, composed of 30–40 amino acid residues, homologous to BmKTX. All these toxins, although being short peptides, are encoded by individual cDNAs, instead of originating from cleavage of a common precursor. Structure The toxin consists of multiple parts. The N- and C- t ...
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Voltage Gated Potassium Channel
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) *Kvα3 ...
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KCNA3
Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the ''KCNA3'' gene. Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes – shaker, shaw, shab, and shal – have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker gene, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the Voltage-gated potassium channel#Delayed rectifier, delayed rectifier class, members of which allow nerve c ...
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Mesobuthus Martensii
''Mesobuthus'' is an Asian genus of scorpions in the family Buthidae The Buthidae are the largest family of scorpions, containing about 100 genera and 1339 species as of 2022. A few very large genera ('' Ananteris'', '' Centruroides'', '' Compsobuthus'', or '' Tityus'') are known, but a high number of species-poor .... Species ''Mesobuthus'' contains the following species: * '' Mesobuthus afghanus'' (Pocock, 1889) * '' Mesobuthus barszczewskii'' (Birula, 1904) * '' Mesobuthus birulai'' Kovarik ''et al.'', 2022 * '' Mesobuthus bogdoensis'' (Birula, 1896) * '' Mesobuthus crucittii'' Kovarik ''et al.'', 2022 * '' Mesobuthus eupeus'' (C.L. Koch, 1839) * '' Mesobuthus fomichevi'' Kovarik ''et al.'', 2022 * '' Mesobuthus farleyi'' Kovarik ''et al.'', 2022 * '' Mesobuthus galinae'' Kovarik ''et al.'', 2022 * '' Mesobuthus haarlovi'' Vachon, 1958 * '' Mesobuthus iranus'' (Birula, 1917) * '' Mesobuthus kaftani'' Kovarik ''et al.'', 2022 * '' Mesobuthus kirmanensis'' (Birula, 1900) * ...
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Kaliotoxin
Kaliotoxin (KTX) inhibits potassium flux through the Kv1.3 voltage-gated potassium channel and calcium-activated potassium channels by physically blocking the channel-entrance and inducing a conformational change in the K+- selectivity filter of the channel. Sources KTX is a neurotoxin derived from the scorpion Androctonus mauretanicus mauretanicus, which is found in the Middle East and North Africa. Chemistry Kaliotoxin is a 4-kDa polypeptide chain, containing 38 amino acids. The formula is . The sequence has a large homology with iberiotoxin from ''Buthus tumulus'', charybdotoxin from ''Leiurus quinquestriatus'' and noxiustoxin from ''Centruroides noxius''. An Important site of the toxin is the K27 side chain (a lysine at place 27 of the protein sequence), which enters the pore and protrudes into the selectivity filter of the channel. Target KTX binds to the Kv1.3 voltage-gated potassium channel and the Calcium-activated potassium channels ( BK channels). These channels co ...
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α-helix
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is also the most extreme type of local structure, and it is the local structure that is most easily predicted from a sequence of amino acids. The alpha helix has a right-handed helix conformation in which every backbone amino, N−H group hydrogen bonds to the backbone carbonyl, C=O group of the amino acid that is four residue (biochemistry), residues earlier in the protein sequence. Other names The alpha helix is also commonly called a: * Pauling–Corey–Branson α-helix (from the names of three scientists who described its structure) * 3.613-helix because there are 3.6 amino acids in one ring, with 13 atoms being involved in the ring formed by the hydrogen bond (starting with amidic hydrogen and ending with carbonyl oxygen) Discovery ...
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β 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. A re ...
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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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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 given substance. 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 higher toxicity. The term LD50 is generally attributed to John William Trevan. 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 expres ...
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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 (e.g. K+ (potassium ion)) while an anion is a negatively charged ion with more electrons than protons (e.g. Cl− (chloride ion The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pro ...) and OH− (hydroxide ion)). Opposite electric charges are pulled towards one another by electrostatic force, so cations and anions attract each other and readily form ionic ...
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