Charybdotoxin
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Charybdotoxin
Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion '' Leiurus quinquestriatus hebraeus'' (''deathstalker'') that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from ''Leiurus quinquestriatus hebraeus''. It is named after Charybdis, a sea monster from Greek myth. Chemical properties Family The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin, derived from the venom of scorpion Pandinus imperator. Structure Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins. Charybdotoxin, a 37 amino acid, 4 kDa neurotoxin with the molecular formula C176H277N57O55S7, is one of the peptide toxins that can be extracted from the venom of the scorpion. Its structure is very similar to that of margatoxin. Charybdotoxin contains three d ...
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Agitoxin
Agitoxin is a toxin found in the venom of the scorpion '' Leiurus quinquestriatus hebraeus'' (yellow scorpion). Other toxins found in this species include charybdotoxin (CTX). CTX is a close homologue of Agitoxin. Structure Agitoxin can be purified using HPLC techniques. Primary structure: Three types of agitoxin can be distinguished, each identified as comprising 38 amino acids. They are highly homologous, differing only in the identity of the residues at positions 7, 15, 29 and 31. *Agitoxin-1 Gly-Val-Pro-Ile-Asn-Val-Lys-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Leu-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Ile-Asn-Gly-Lys-Cys-His-Cys-Thr-Pro-Lys (GVPINVKCTGSPQCLKPCKDAGMRFGKCINGKCHCTPK, molecular weight = 4014.87 Da, molecular formula = C169H278N52O47S7) *Agitoxin-2 Gly-Val-Pro-Ile-Asn-Val-Ser-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Ile-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-His-Cys-Thr-Pro-Lys (GVPINVSCTGSPQCIKPCKDAGMRFGKCMNRKCHCTPK, molecular weight ...
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Potassium Channels
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 regulate ce ...
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Margatoxin
Margatoxin (MgTX) is a peptide that selectively inhibits Kv1.3 voltage-dependent potassium channels. It is found in the venom of ''Centruroides margaritatus'', also known as the Central American Bark Scorpion. Margatoxin was first discovered in 1993. It was purified from scorpion venom and its amino acid sequence was determined. Structure Margatoxin is a peptide of 39 amino acids with a molecular weight of 4185 Dalton. The primary amino acid sequence of margatoxin is as follows: : Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser-Pro-Lys-Gln-Cys-Leu-Pro-Pro-Cys-Lys-Ala-Gln-Phe-Gly-Gln-Ser-Ala-Gly-Ala-Lys-Cys-Met-Asn-Gly-Lys-Cys-Lys-Cys-Tyr-Pro-His Or, when translated to one-letter sequence, :TIINVKCTSPKQCLPPCKAQFGQSAGAKCMNGKCKCYPH. There are disulfide bridges between Cys7-Cys29, Cys13-Cys34 and Cys17-Cys36. Margatoxin is classified as a "scorpion short toxin" by Pfam, showing sequence homology with other potassium channel blockers, such as charybdotoxin (44%), kaliotoxin (54%), iberiotoxin ...
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Pandinotoxin
Pandinotoxins are toxins from the venom of the emperor scorpion '' Pandinus imperator''. They are selective blockers of voltage-gated potassium channels Sources The source for the pandinotoxins is the venom of the scorpion '' Pandinus imperator''. Chemistry Family The toxins of the family are designated pandinotoxin (PiTX)-Kα, PiTX-Kβ, and PiTX-Kγ They are members of the α-KTx family of scorpion toxins. Structure and homology Pandinotoxin Kα and -β The amino acid sequences of PiTX-K α and PiTX-K β are identical, except for the seventh amino acid: a proline in PiTX-Kα and a glutamic acid in PiTX-Kβ (see Fig.1). PiTX-Kα and PiTX-Kβ are 35-residue peptides, which are found to have an α-helix from residues 10 to 21 and two β-sheets (β 1 is from residues 26-28, β 2 is from residues 33-35). One face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). PiTX-K α and PiT ...
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Protein Data Bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations (PDBe, PDBj, RCSB, and BMRB). The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB. The PDB is a key in areas of structural biology, such as structural genomics. Most major scientific journals and some funding agencies now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB. For example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. History Two force ...
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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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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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Alpha Blockers
Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , which is the West Semitic word for " ox". Letters that arose from alpha include the Latin letter A and the Cyrillic letter А. Uses Greek In Ancient Greek, alpha was pronounced and could be either phonemically long ( ː or short ( . Where there is ambiguity, long and short alpha are sometimes written with a macron and breve today: Ᾱᾱ, Ᾰᾰ. * ὥρα = ὥρᾱ ''hōrā'' "a time" * γλῶσσα = γλῶσσᾰ ''glôssa'' "tongue" In Modern Greek, vowel length has been lost, and all instances of alpha simply represent the open front unrounded vowel . In the polytonic orthography of Greek, alpha, like other vowel letters, can occur with several diacritic marks: any of three accent symbols (), and either of two breathing marks ...
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Shaker Gene
The ''shaker (Sh)'' gene, when mutated, causes a variety of atypical behaviors in the fruit fly, ''Drosophila melanogaster''. Under ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs. In ''Drosophila'', the shaker gene is located on the X chromosome. The closest human homolog is KCNA3. Function The ''Sh'' gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell. A working shaker channel is voltage-dependent and has four subunits, which form a pore through which ions flow, carrying type-A potassium current (IA). A mutation in the Sh gene reduces the conductance of charge across the neuron si ...
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Disulfide Bridge
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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Pandinus Imperator
The emperor scorpion, ''Pandinus imperator'', is a species of scorpion native to rainforests and savannas in West Africa. It is one of the largest scorpions in the world and lives for 6–8 years. Its body is black, but like other scorpions it glows pastel green or blue under ultraviolet light. It is a popular species in the pet trade, and is protected by CITES to prevent over-collecting that might impact the species' survival. Description The emperor scorpion (''Pandinus imperator'') is one of the largest species of scorpion in the world, with adults averaging about in length and a weight of 30 g. However, some species of forest scorpions are fairly similar to the emperor scorpion in size, and one scorpion, ''Heterometrus swammerdami'', holds the record for being the world's largest scorpion at 9 inches (23 cm) in length. The large pincers are blackish-red and have a granular texture. The front part of the body, or prosoma, is made up of four sections, each with a p ...
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