Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
A genus of cone-shaped marine snails in the family Conidae, class GASTROPODA. It comprises more than 600 species, many containing unique venoms (CONUS VENOMS) with which they immobilize their prey.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule. (1/410)

While studying the adult rat skeletal muscle Na+ channel outer vestibule, we found that certain mutations of the lysine residue in the domain III P region at amino acid position 1237 of the alpha subunit, which is essential for the Na+ selectivity of the channel, produced substantial changes in the inactivation process. When skeletal muscle alpha subunits (micro1) with K1237 mutated to either serine (K1237S) or glutamic acid (K1237E) were expressed in Xenopus oocytes and depolarized for several minutes, the channels entered a state of inactivation from which recovery was very slow, i.e., the time constants of entry into and exit from this state were in the order of approximately 100 s. We refer to this process as "ultra-slow inactivation". By contrast, wild-type channels and channels with the charge-preserving mutation K1237R largely recovered within approximately 60 s, with only 20-30% of the current showing ultra-slow recovery. Coexpression of the rat brain beta1 subunit along with the K1237E alpha subunit tended to accelerate the faster components of recovery from inactivation, as has been reported previously of native channels, but had no effect on the mutation-induced ultra-slow inactivation. This implied that ultra-slow inactivation was a distinct process different from normal inactivation. Binding to the pore of a partially blocking peptide reduced the number of channels entering the ultra-slow inactivation state, possibly by interference with a structural rearrangement of the outer vestibule. Thus, ultra-slow inactivation, favored by charge-altering mutations at site 1237 in micro1 Na+ channels, may be analogous to C-type inactivation in Shaker K+ channels.  (+info)

NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors. (2/410)

A 600 MHz NMR study of alpha-conotoxin ImI from Conus imperialis, targeting the alpha7 neuronal nicotinic acetylcholine receptor (nAChR), is presented. ImI backbone spatial structure is well defined basing on the NOEs, spin-spin coupling constants, and amide protons hydrogen-deuterium exchange data: rmsd of the backbone atom coordinates at the 2-12 region is 0.28 A in the 20 best structures. The structure is described as a type I beta-turn (positions 2-5) followed by a distorted helix (positions 5-11). Similar structural patterns can be found in all neuronal-specific alpha-conotoxins. Highly mobile side chains of the Asp-5, Arg-7 and Trp-10 residues form a single site for ImI binding to the alpha7 receptor. When depicted with opposite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these structural elements appearing essential for binding to the neuronal nAChRs.  (+info)

A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx. (3/410)

Cone snails are gastropod mollusks of the genus Conus that live in tropical marine habitats. They are predators that paralyze their prey by injection of venom containing a plethora of small, conformationally constrained peptides (conotoxins). We report the identification, characterization, and structure of a gamma-carboxyglutamic acid-containing peptide, conotoxin epsilon-TxIX, isolated from the venom of the molluscivorous cone snail, Conus textile. The disulfide bonding pattern of the four cysteine residues, an unparalleled degree of posttranslational processing including bromination, hydroxylation, and glycosylation define a family of conotoxins that may target presynaptic Ca2+ channels or act on G protein-coupled presynaptic receptors via another mechanism. This conotoxin selectively reduces neurotransmitter release at an Aplysia cholinergic synapse by reducing the presynaptic influx of Ca2+ in a slow and reversible fashion. The three-dimensional structure, determined by two-dimensional 1H NMR spectroscopy, identifies an electronegative patch created by the side chains of two gamma-carboxyglutamic acid residues that extend outward from a cavernous cleft. The glycosylated threonine and hydroxylated proline enclose a localized hydrophobic region centered on the brominated tryptophan residue within the constrained intercysteine region.  (+info)

Solution structure of alpha-conotoxin ImI determined by two-dimensional NMR spectroscopy. (4/410)

The three-dimensional structure of alpha-conotoxin ImI, a potent antagonist targeting the neuronal alpha7 subtype of nicotinic acetylcholine receptor (nAChR), has been investigated by NMR spectroscopy. On the basis of 181 experimental constraints, a total of 25 converged structures were obtained. The average pairwise atomic root mean square difference is 0.40+/-0.11 A for the backbone atoms. The resulting structure indicates the presence of two successive type I beta-turns and a 310 helix for residues Cys2-Cys8 and Ala9-Arg11, respectively, and shows a significant structural similarity to that of alpha-conotoxin PnIA, which is also selective for the neuronal nAChR.  (+info)

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. (5/410)

The present work uses alpha-conotoxin ImI (CTx ImI) to probe the neurotransmitter binding site of neuronal alpha7 acetylcholine receptors. We identify key residues in alpha7 that contribute to CTx ImI affinity, and use mutant cycles analysis to identify pairs of residues that stabilize the receptor-conotoxin complex. We first mutated key residues in the seven known loops of alpha7 that converge at the subunit interface to form the ligand binding site. The mutant subunits were expressed in 293 HEK cells, and CTx ImI binding was measured by competition against the initial rate of 125I-alpha-bungarotoxin binding. The results reveal a predominant contribution by Tyr-195 in alpha7, accompanied by smaller contributions by Thr-77, Tyr-93, Asn-111, Gln-117, and Trp-149. Based upon our previous identification of bioactive residues in CTx ImI, we measured binding of receptor and toxin mutations and analyzed the results using thermodynamic mutant cycles. The results reveal a single dominant interaction between Arg-7 of CTx ImI and Tyr-195 of alpha7 that anchors the toxin to the binding site. We also find multiple weak interactions between Asp-5 of CTx ImI and Trp-149, Tyr-151, and Gly-153 of alpha7, and between Trp-10 of CTx ImI and Thr-77 and Asn-111 of alpha7. The overall results establish the orientation of CTx ImI as it bridges the subunit interface and demonstrate close approach of residues on opposing faces of the alpha7 binding site.  (+info)

Acetylcholine and epibatidine binding to muscle acetylcholine receptors distinguish between concerted and uncoupled models. (6/410)

The muscle acetylcholine receptor (AChR) has served as a prototype for understanding allosteric mechanisms of neurotransmitter-gated ion channels. The phenomenon of cooperative agonist binding is described by the model of Monod et al. (Monod, J., Wyman, J., and Changeux, J. P. (1965) J. Mol. Biol. 12, 88-118; MWC model), which requires concerted switching of the two binding sites between low and high affinity states. The present study examines binding of acetylcholine (ACh) and epibatidine, agonists with opposite selectivity for the two binding sites of mouse muscle AChRs. We expressed either fetal or adult AChRs in 293 HEK cells and measured agonist binding by competition against the initial rate of 125I-alpha-bungarotoxin binding. We fit predictions of the MWC model to epibatidine and ACh binding data simultaneously, taking as constants previously determined parameters for agonist binding and channel gating steps, and varying the agonist-independent parameters. We find that the MWC model describes the apparent dissociation constants for both agonists but predicts Hill coefficients that are far too steep. An Uncoupled model, which relaxes the requirement of concerted state transitions, accurately describes binding of both ACh and epibatidine and provides parameters for agonist-independent steps consistent with known aspects of AChR function.  (+info)

The block of Shaker K+ channels by kappa-conotoxin PVIIA is state dependent. (7/410)

kappa-conotoxin PVIIA is the first conotoxin known to interact with voltage-gated potassium channels by inhibiting Shaker-mediated currents. We studied the mechanism of inhibition and concluded that PVIIA blocks the ion pore with a 1:1 stoichiometry and that binding to open or closed channels is very different. Open-channel properties are revealed by relaxations of partial block during step depolarizations, whereas double-pulse protocols characterize the slower reequilibration of closed-channel binding. In 2.5 mM-[K+]o, the IC50 rises from a tonic value of approximately 50 to approximately 200 nM during openings at 0 mV, and it increases e-fold for about every 40-mV increase in voltage. The change involves mainly the voltage dependence and a 20-fold increase at 0 mV of the rate of PVIIA dissociation, but also a fivefold increase of the association rate. PVIIA binding to Shaker Delta6-46 channels lacking N-type inactivation or to wild phenotypes appears similar, but inactivation partially protects the latter from open-channel unblock. Raising [K+]o to 115 mM has little effect on open-channel binding, but increases almost 10-fold the tonic IC50 of PVIIA due to a decrease by the same factor of the toxin rate of association to closed channels. In analogy with charybdotoxin block, we attribute the acceleration of PVIIA dissociation from open channels to the voltage-dependent occupancy by K+ ions of a site at the outer end of the conducting pore. We also argue that the occupancy of this site by external cations antagonizes on binding to closed channels, whereas the apparent competition disappears in open channels if the competing cation can move along the pore. It is concluded that PVIIA can also be a valuable tool for probing the state of ion permeation inside the pore.  (+info)

A marine snail neurotoxin shares with scorpion toxins a convergent mechanism of blockade on the pore of voltage-gated K channels. (8/410)

kappa-Conotoxin-PVIIA (kappa-PVIIA) belongs to a family of peptides derived from a hunting marine snail that targets to a wide variety of ion channels and receptors. kappa-PVIIA is a small, structurally constrained, 27-residue peptide that inhibits voltage-gated K channels. Three disulfide bonds shape a characteristic four-loop folding. The spatial localization of positively charged residues in kappa-PVIIA exhibits strong structural mimicry to that of charybdotoxin, a scorpion toxin that occludes the pore of K channels. We studied the mechanism by which this peptide inhibits Shaker K channels expressed in Xenopus oocytes with the N-type inactivation removed. Chronically applied to whole oocytes or outside-out patches, kappa-PVIIA inhibition appears as a voltage-dependent relaxation in response to the depolarizing pulse used to activate the channels. At any applied voltage, the relaxation rate depended linearly on the toxin concentration, indicating a bimolecular stoichiometry. Time constants and voltage dependence of the current relaxation produced by chronic applications agreed with that of rapid applications to open channels. Effective valence of the voltage dependence, zdelta, is approximately 0.55 and resides primarily in the rate of dissociation from the channel, while the association rate is voltage independent with a magnitude of 10(7)-10(8) M-1 s-1, consistent with diffusion-limited binding. Compatible with a purely competitive interaction for a site in the external vestibule, tetraethylammonium, a well-known K-pore blocker, reduced kappa-PVIIA's association rate only. Removal of internal K+ reduced, but did not eliminate, the effective valence of the toxin dissociation rate to a value <0.3. This trans-pore effect suggests that: (a) as in the alpha-KTx, a positively charged side chain, possibly a Lys, interacts electrostatically with ions residing inside the Shaker pore, and (b) a part of the toxin occupies an externally accessible K+ binding site, decreasing the degree of pore occupancy by permeant ions. We conclude that, although evolutionarily distant to scorpion toxins, kappa-PVIIA shares with them a remarkably similar mechanism of inhibition of K channels.  (+info)

Conotoxins are a group of peptide toxins found in the venom of cone snails (genus Conus). These toxins are synthesized and stored in the venom ducts of the snails and are used for prey capture or defense against predators. Conotoxins have diverse pharmacological activities, acting on various ion channels and receptors in the nervous system. They are characterized by their small size (10-30 amino acids), disulfide bonding pattern, and high sequence variability. Due to their specificity and potency, conotoxins have been studied as potential leads for the development of novel therapeutics, particularly in the areas of pain management and neurological disorders.

A Conus snail, also known as a cone snail, is a type of predatory sea snail that belongs to the family Conidae. These snails are known for their venomous harpoons, which they use to capture and immobilize prey. The venom of some species can be dangerous or even deadly to humans.

Conus snails are found in tropical and subtropical waters around the world, and there are over 700 different species. They vary in size, with some species measuring just a few millimeters long and others reaching lengths of several inches. Many Conus snails have brightly colored shells that are highly prized by collectors.

In addition to their medical significance as a source of venom, Conus snails are also of interest to researchers because they produce a variety of bioactive compounds that have potential applications in medicine. For example, some cone snail venoms contain peptides that have been shown to have pain-relieving and neuroprotective properties.

Mollusk venoms are toxic substances produced by certain species of mollusks, a group of marine animals that includes snails, slugs, clams, octopuses, and squids. These venoms are primarily used for defense against predators or for hunting prey. They can contain a variety of bioactive molecules, such as proteins, peptides, and neurotoxins, which can cause a range of effects on the victim's body, from mild irritation to paralysis and death.

One well-known example of a mollusk venom is that of the cone snail, which uses its venom to capture prey. The venom of some cone snails contains compounds called conotoxins, which are highly selective for specific ion channels in the nervous system and can cause paralysis or death in their victims. These conotoxins have been studied for their potential therapeutic applications, such as pain relief and treatment for neurological disorders.

It's important to note that while some mollusk venoms can be dangerous or even deadly to humans, most species of mollusks are not harmful to people. However, it's always a good idea to exercise caution when handling any marine animals, as even non-venomous species can cause injury with their sharp shells or other structures.

I'm sorry for any confusion, but the term "snails" is not a medical term. It is a common name used to refer to a large group of land and sea-dwelling mollusks that have coiled shells and move slowly by means of a muscular foot. If you have any questions about medical terminology or health-related topics, I'd be happy to help! Just let me know what you're looking for.

Nicotinic antagonists are a class of drugs that block the action of nicotine at nicotinic acetylcholine receptors (nAChRs). These receptors are found in the nervous system and are activated by the neurotransmitter acetylcholine, as well as by nicotine. When nicotine binds to these receptors, it can cause the release of various neurotransmitters, including dopamine, which can lead to rewarding effects and addiction.

Nicotinic antagonists work by binding to nAChRs and preventing nicotine from activating them. This can help to reduce the rewarding effects of nicotine and may be useful in treating nicotine addiction. Examples of nicotinic antagonists include mecamylamine, varenicline, and cytisine.

It's important to note that while nicotinic antagonists can help with nicotine addiction, they can also have side effects, such as nausea, vomiting, and abnormal dreams. Additionally, some people may experience more serious side effects, such as seizures or cardiovascular problems, so it's important to use these medications under the close supervision of a healthcare provider.

Disulfides are a type of organic compound that contains a sulfur-sulfur bond. In the context of biochemistry and medicine, disulfide bonds are often found in proteins, where they play a crucial role in maintaining their three-dimensional structure and function. These bonds form when two sulfhydryl groups (-SH) on cysteine residues within a protein molecule react with each other, releasing a molecule of water and creating a disulfide bond (-S-S-) between the two cysteines. Disulfide bonds can be reduced back to sulfhydryl groups by various reducing agents, which is an important process in many biological reactions. The formation and reduction of disulfide bonds are critical for the proper folding, stability, and activity of many proteins, including those involved in various physiological processes and diseases.

Cystine is a naturally occurring amino acid in the body, which is formed from the oxidation of two cysteine molecules. It is a non-essential amino acid, meaning that it can be produced by the body and does not need to be obtained through diet. Cystine plays important roles in various biological processes, including protein structure and antioxidant defense. However, when cystine accumulates in large amounts, it can form crystals or stones, leading to conditions such as cystinuria, a genetic disorder characterized by the formation of cystine kidney stones.

Neurotoxins are substances that are poisonous or destructive to nerve cells (neurons) and the nervous system. They can cause damage by destroying neurons, disrupting communication between neurons, or interfering with the normal functioning of the nervous system. Neurotoxins can be produced naturally by certain organisms, such as bacteria, plants, and animals, or they can be synthetic compounds created in a laboratory. Examples of neurotoxins include botulinum toxin (found in botulism), tetrodotoxin (found in pufferfish), and heavy metals like lead and mercury. Neurotoxic effects can range from mild symptoms such as headaches, muscle weakness, and tremors, to more severe symptoms such as paralysis, seizures, and cognitive impairment. Long-term exposure to neurotoxins can lead to chronic neurological conditions and other health problems.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Sodium channel blockers are a class of medications that work by blocking sodium channels in the heart, which prevents the rapid influx of sodium ions into the cells during depolarization. This action slows down the rate of impulse generation and propagation in the heart, which in turn decreases the heart rate and prolongs the refractory period.

Sodium channel blockers are primarily used to treat cardiac arrhythmias, including atrial fibrillation, atrial flutter, and ventricular tachycardia. They may also be used to treat certain types of neuropathic pain. Examples of sodium channel blockers include Class I antiarrhythmics such as flecainide, propafenone, lidocaine, and mexiletine.

It's important to note that sodium channel blockers can have potential side effects, including proarrhythmia (i.e., the development of new arrhythmias or worsening of existing ones), negative inotropy (decreased contractility of the heart muscle), and cardiac conduction abnormalities. Therefore, these medications should be used with caution and under the close supervision of a healthcare provider.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Nicotinic receptors are a type of ligand-gated ion channel receptor that are activated by the neurotransmitter acetylcholine and the alkaloid nicotine. They are widely distributed throughout the nervous system and play important roles in various physiological processes, including neuronal excitability, neurotransmitter release, and cognitive functions such as learning and memory. Nicotinic receptors are composed of five subunits that form a ion channel pore, which opens to allow the flow of cations (positively charged ions) when the receptor is activated by acetylcholine or nicotine. There are several subtypes of nicotinic receptors, which differ in their subunit composition and functional properties. These receptors have been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.

Peptides are short chains of amino acid residues linked by covalent bonds, known as peptide bonds. They are formed when two or more amino acids are joined together through a condensation reaction, which results in the elimination of a water molecule and the formation of an amide bond between the carboxyl group of one amino acid and the amino group of another.

Peptides can vary in length from two to about fifty amino acids, and they are often classified based on their size. For example, dipeptides contain two amino acids, tripeptides contain three, and so on. Oligopeptides typically contain up to ten amino acids, while polypeptides can contain dozens or even hundreds of amino acids.

Peptides play many important roles in the body, including serving as hormones, neurotransmitters, enzymes, and antibiotics. They are also used in medical research and therapeutic applications, such as drug delivery and tissue engineering.

Protein folding is the process by which a protein molecule naturally folds into its three-dimensional structure, following the synthesis of its amino acid chain. This complex process is determined by the sequence and properties of the amino acids, as well as various environmental factors such as temperature, pH, and the presence of molecular chaperones. The final folded conformation of a protein is crucial for its proper function, as it enables the formation of specific interactions between different parts of the molecule, which in turn define its biological activity. Protein misfolding can lead to various diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

"Xenopus" is not a medical term, but it is a genus of highly invasive aquatic frogs native to sub-Saharan Africa. They are often used in scientific research, particularly in developmental biology and genetics. The most commonly studied species is Xenopus laevis, also known as the African clawed frog.

In a medical context, Xenopus might be mentioned when discussing their use in research or as a model organism to study various biological processes or diseases.

In genetics, sequence alignment is the process of arranging two or more DNA, RNA, or protein sequences to identify regions of similarity or homology between them. This is often done using computational methods to compare the nucleotide or amino acid sequences and identify matching patterns, which can provide insight into evolutionary relationships, functional domains, or potential genetic disorders. The alignment process typically involves adjusting gaps and mismatches in the sequences to maximize the similarity between them, resulting in an aligned sequence that can be visually represented and analyzed.

Daly NL, Craik DJ (February 2009). "Structural studies of conotoxins". IUBMB Life. 61 (2): 144-50. doi:10.1002/iub.158. PMID ... Such proteins include C1q, elastins, PrP, Argonaute 2, and conotoxins, among others. As prolyl hydroxylase requires ascorbate ...
All conorfamides are disulfide-poor conotoxins. CNF-Sr3 shares 73.3% sequence similarity with CNF-Sr1 and 31.0% sequence ...
Conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a ... One of the unique forms of conotoxins, ω-conotoxin (ω-CgTx) is highly specific for Ca channels and has shown usefulness in ... In many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, ... Jacob, Reed B.; McDougal, Owen M. (2010). "The M-superfamily of Conotoxins: a Review". Cellular and Molecular Life Sciences. 67 ...
These toxins are known as conotoxins or conopeptides. The toxins are of importance to medical research. A notable feature of ...
Their venom contains conotoxins which have powerful neurotoxic effects. Given that they are capable of "stinging" humans, live ...
Buczek O, Bulaj G, Olivera BM (December 2005). "Conotoxins and the posttranslational modification of secreted gene products". ...
Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu-conotoxins target the ... whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. ... The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ( ... Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of ...
ω-Conotoxins are derived from the venom of cone snails. ω-Conotoxin MVIIC acts within the hippocampal CA1 pyramidal neurons to ...
"Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
The Conus Biodiversity website Cone Shell and Conotoxins website Pain Killer Comes out of its Shell - The Age 25 July 2005 ... "Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
... neosaxitoxin and several of the conotoxins also bind the same site. The use of this toxin as a biochemical probe has elucidated ...
Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences. Hydroxylation of proline has been ...
Biodiversity-Derived Discovery of Novel Sodium Channel Blocking Conotoxins from Conus bullatus". Toxicon. 53 (1): 90-8. doi: ...
"The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels". The ...
These molecules, called conotoxins, led to a breakthrough in the study of ion channels and neuromuscular synapses. He ...
The appeal of conotoxins for creating pharmaceutical drugs is the precision and speed with which the chemicals act; many of the ... The toxins in cone snail venom are referred to as conotoxins, and are composed of various peptides, each targeting a specific ... Natural History Museum Rotterdam - photos of Conus shells Cone snail and conotoxins page The Conus Biodiversity website ...
HWTX-X has selectivity for isoforms of N-type Ca2+ channels, compared with ω-conotoxins GVIA and MVIIA. HWTX-X specifically ... While structurally similar to ω-conotoxins that block the twitch response to electrical nerve stimulation, HWTX-X has no effect ...
The Waglerins and complementary conotoxins are useful tools to discover the contribution of acetylcholine receptor subunits to ... "Definition and Characterization of the Short alphaA-Conotoxins: A Single Residue Determines Dissociation Kinetics from the ...
Although many N-type calcium channels blockers are known, most potent and selective belong to the family of conotoxins. List of ... a synthetic version of one of conotoxins Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2019-09-16). "Voltage-gated ... although the most notable blockers are ω-conotoxins. N-type calcium channels are categorized as high threshold-activated ... N-type Calcium channel blockers: ω-Conotoxins Cadmium Caroverine Cilnidipine Desipramine Gabapentin nonselectively inhibits N- ...
Her work focused on the isolation of peptides from the conotoxins in the snail's venom while their effects were still unknown. ... She has also contributed to the development of conotoxins as tools for examining the activity of the human brain. Her ... Her research shed light on the effects of conotoxins on the central nervous system and their connection to muscular paralysis, ... For example, two classes of conotoxins are used as analytical agents: ω-conotoxin has been widely used for studying neuronal ...
Since it has a structural similarity to the ω-conotoxins, it is possible that their blocking mechanism is similar. MVIIA is a ... and N-termini The structure of Ptu1 is slightly homologous with the ω-conotoxins.: Geographus Venom IA (GVIA) and Mollusc Venom ...
... s typically lack disulfide bonds, in contrast to most families of conotoxins, which have an unusually high density of ...
They are relatively homologous to the calcium channel blockers omega-conotoxins from marine cone snails and belong to the four- ...
... is also functionally similar to delta-conotoxins, which binds to the receptor site 6 of voltage-gated sodium channel, ...
C. regius is known to have more different conotoxins than any other Cone sail species, its conotoxin it's potentially of ...
It is thought that the conotoxins in the venom of cone snails are able to completely relax this muscle so that the body can be ...
Zugasti-Cruz, A., Aguilar, M.B., Falcon, A., Olivera, B.M., & Heimer de la Cotera, E.P. (2008) Two new 4-cys conotoxins ( ...
Cruz is recognized as one of the five laureates of L'Oreal-UNESCO Awards for Women in Science for the discovery of conotoxins ...
... knot motif that is formed by the cysteine residues shows analogy to other spider toxins and can also be found in ω-conotoxins, ...
... conotoxins MeSH D20.888.590.162.720 - omega-conotoxins MeSH D20.888.590.162.720.700 - omega-conotoxin gvia MeSH D20.888.590.325 ...
define omega-Conotoxins. Explain omega-Conotoxins. What is omega-Conotoxins? omega-Conotoxins FAQ. ... omega-Conotoxins. Medical Dictionary -> omega-Conotoxins. Search: omega-Conotoxins. A family of structurally related neurotoxic ...
Daly NL, Craik DJ (February 2009). "Structural studies of conotoxins". IUBMB Life. 61 (2): 144-50. doi:10.1002/iub.158. PMID ... Such proteins include C1q, elastins, PrP, Argonaute 2, and conotoxins, among others. As prolyl hydroxylase requires ascorbate ...
Submitted by Ronald L. Bridges. Kansas State University researchers are asked to review inventories and notify the University Select Agent Program if using any listed biological toxins.. The U.S. government has been closely watching the transfer of certain biological organisms and toxins to combat terrorism since 1995. The Select Agent Program was developed to regulate the possession, use and transfer of biological agents and toxins that could pose a severe threat to public health and safety. Through the years, the program has changed to keep up with science, to remove research barriers and to simplify coordination between agencies.. In late 2012, the departments of Heath and Human Services and Agriculture published final rules amending regulations that govern the possession, use and transfer of select agents and toxins - see 42 C.F.R. Part 73, 7 C.F.R. Part 331 and 9 C.F.R. Part 121. Among the changes are new requirements for transferring select agent toxins, regardless of the quantity.. A ...
14 HEINEMANN SH., LEIPOLD E. Conotoxins of the O-superfamily affecting voltage-gated sodium channels. Cell Mol. Life Sci., 2007 ... Conotoxins as research tools and drug leads. Curr. Protein Pept. Sci., 2005, 6, 221-40. ... Conotoxins as selective inhibitors of neuronal ion channels, receptors and transporters. IUBMB Life., 2004, 56, 89-93. ... 2 AGUILAR MB., LOPEZ-VERA E., HEIMER DE LA COTERA EP., FALCON A., OLIVERA BM., MAILLO M. I-conotoxins in vermivorous species of ...
Novel ω-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. RJ Lewis, KJ Nielsen, DJ Craik, ML ... Conotoxins: chemistry and biology. AH Jin, M Muttenthaler, S Dutertre, SWA Himaya, Q Kaas, DJ Craik, ... ... Discovery, Synthesis, and Structure-Activity Relationships of Conotoxins. KB Akondi, M Muttenthaler, S Dutertre, Q Kaas, DJ ...
S-conotoxins - Inhibit 5-HT3 channels Y-conotoxins - Competitively block muscle acetylcholine receptors ... Venom, with different conotoxins formed rapidly in various portions of the venom duct due to different conotoxin gene ... Several conotoxins, and their synthetic derivatives, due to their high selectivity and affinity for different ion channels, are ... 17] C geographus, which produces the most potent conotoxins found to date, may produce rapid cerebral edema, coma, respiratory ...
... the omega-conotoxins and omega-agatoxins. Annu. Rev. Biochem. 63, 823-867. doi: 10.1146/annurev.biochem.63.1.823 ...
The venom contains proteins called conotoxins that can rapidly cause paralysis, coma, and death. ...
Thus, α-conotoxins are excellent probes to evaluate the functional roles of nAChRs subtypes. We isolated an α4/7-conotoxin ( ... The 3D structure of RegIIA reveals the typical folding of most α4/7-conotoxins. Thus, while structurally related to other α4/7 ... conotoxins, RegIIA has an exquisite balance of shape, charge, and polarity exposed in its structure to potently block the α3β4 ... α-Conotoxins, disulfide-constrained peptides isolated from the venom of cone snails, potently inhibit nAChRs. Their selectivity ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
OMEGA-CONOTOXINS OMEGA-CONOTOXINAS ORGANIZADORES EMBRIÔNICOS ORGANIZERS, EMBRYONIC ORGANIZADORES EMBRIONARIOS OXALOBACTER ...
OMEGA-CONOTOXINS OMEGA-CONOTOXINAS ORGANIZADORES EMBRIÔNICOS ORGANIZERS, EMBRYONIC ORGANIZADORES EMBRIONARIOS OXALOBACTER ...
OMEGA-CONOTOXINS OMEGA-CONOTOXINAS ORGANIZADORES EMBRIÔNICOS ORGANIZERS, EMBRYONIC ORGANIZADORES EMBRIONARIOS OXALOBACTER ...
The sequence diverges from that of previously isolated α-conotoxins. We demonstrate that this structural divergence has ... The sequence diverges from that of previously isolated α-conotoxins. We demonstrate that this structural divergence has ... The sequence diverges from that of previously isolated α-conotoxins. We demonstrate that this structural divergence has ... The sequence diverges from that of previously isolated α-conotoxins. We demonstrate that this structural divergence has ...
Class of small peptides (17 21 residues) from Conus spp. that inhibit NMDA class of glutamate receptors
and Bern,M. (2012) Constrained de novo sequencing of conotoxins. J. Proteome Res. 11:4191-4200. ... the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David ...
Unbricked neutralise port ofloxacin dog eye drops the gunfights off Conotoxins; uveitis, avellan plus myelocystocele. ...
Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of mu-conotoxins PIIIA and ... μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. The ... To explore the mechanism of PIIIA specificity, a double mutant of NaV1.4 mimicking NaV channels resistant to μ-conotoxins and ... Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural ...
Framework perseverance of -CnIIIC uncovered some commonalities to -conotoxins functioning on nAChRs. Bottom line AND ... or conotoxins) focus on numerous and different molecular entities with high affinity and specificity, including voltage- and ...
Conotoxins are widely distributed and important for studying ligand-gated ion channels. TxIB, a conotoxin consisting of 16 ...
μ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution ... μ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution ... GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of μ-conotoxins GIIIA and ...
T-1-family conotoxins belong to the T-superfamily and are composed of 10-17 amino acids. They share a common cysteine framework ...
I currently work in the Olivera Lab, where I focus on characterizing conotoxins, or neurotoxic peptides isolated from cone ...
... cysteine pairing in disulfide bonded conotoxins. Anal. Chem. 82:8313-8319. ... the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David ...
Upon investigation, the samples were determined to contain various levels of venom components such as conotoxins, ...
... whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. The ... The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel ...
  • Modern Conus research has primarily focused on purifying and characterizing the toxins from the venom apparatus and on demonstrating that the poison from an individual cone snail contains several toxins, mostly small peptides (conotoxins) that target specific isoforms of receptors or ion channels (3, 6, 20, 25, 27, 35). (scielo.br)
  • α-Conotoxins, disulfide-constrained peptides isolated from the venom of cone snails, potently inhibit nAChRs. (edu.au)
  • Gupta,K. and Balaram,P. (2010) Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins. (conoserver.org)
  • Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). (smartox-biotech.com)
  • Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by mu-conotoxins. (smartox-biotech.com)
  • The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. (emeco.es)
  • μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. (smartox-biotech.com)
  • The results derived from both investigations indicate some differences between conotoxins and venom components found in other toxoglossates. (scielo.br)
  • Upon investigation, the samples were determined to contain various levels of venom components such as conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins. (planet-today.com)
  • To explore the mechanism of PIIIA specificity, a double mutant of NaV1.4 mimicking NaV channels resistant to μ-conotoxins and tetrodotoxin is constructed and the binding of PIIIA to this mutant channel examined. (smartox-biotech.com)
  • Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX-resistant VSSC current in sensory ganglion neurons. (smartox-biotech.com)
  • Thus, α-conotoxins are excellent probes to evaluate the functional roles of nAChRs subtypes. (edu.au)
  • Conopeptides (or conotoxins) focus on numerous and different molecular entities with high affinity and specificity, including voltage- and ligand-gated ion stations, and G-protein-coupled receptors (McIntosh Pursuing chemical synthesis of the peptide identical towards the indigenous product, the artificial -conotoxin CnIIIC was examined on several arrangements and molecular goals to assess its potential being a myorelaxant. (cancer-ecosystem.com)
  • The sequence diverges from that of previously isolated α-conotoxins. (nau.edu)
  • The sequence of the peptide is: Arg-Asp-Hyp-Cys-Cys-Tyr- His-Pro-Thr-Cys-Asn-Met-Ser-Asn-Pro-Gln-Ile-Cys-NH 2 , with disulfide bridging between Cys4-Cys10 and Cys5-Cys18, analogous to those of previously described α-conotoxins. (nau.edu)
  • The major trans conformation results in a three-dimensional structure that is significantly different from the previously identified conformation of mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. (smartox-biotech.com)
  • The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. (conoserver.org)
  • Conotoxins are widely distributed and important for studying ligand-gated ion channels. (bvsalud.org)
  • A subset of these peptides known as α-conotoxins, are antagonists of nicotinic acetylcholine receptors (nAChRs). (frontiersin.org)
  • 6. Orthosteric and/or Allosteric Binding of α-Conotoxins to Nicotinic Acetylcholine Receptors and Their Models. (nih.gov)
  • 8. Globular and ribbon isomers of Conus geographus α-conotoxins antagonize human nicotinic acetylcholine receptors. (nih.gov)
  • Classification of conotoxins obtained from Indian Conus species in their putative superfamily (protein) according to their sequence. (ncbs.res.in)
  • Several Conus-derived venom peptides are promising lead compounds for the management of neuropathic pain, with α-conotoxins being of particular interest. (applerefurbished.eu)
  • In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. (nih.gov)
  • 9. Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins. (nih.gov)
  • Conotoxins, found in the venom of marine snails, are small cysteine rich peptides whose sequences and structural features have been found to dictate selectivity between closely related receptors (α-CTxMII[E11A] for the α 6 α 4 β 2 β 3 α-CTxLvIA for α 3 β 2 -nAChR, α-CTxBuIA for α 3 β 4 -nAChR, and the µ-CTxGIIIA for Na v 1.4). (boisestate.edu)
  • Chapter one discusses how wild-type and mutant conotoxins have been discovered and used to elucidate selectivity, and therefore tertiary binding paradigms for closely related ion pore receptor isoforms. (boisestate.edu)
  • Research report finding toxin -like peptides similar to those in animal venom (conotoxins, phospholipsases, phosphodiesterases, zinc metal proteinases, and bradykinins) were found in fecal samples from COVID-19 patients, but not in control patients. (campfire.wiki)
  • Targeted re-engineering of native α-conotoxins has resulted in excellent tools for nAChR research as well as potential therapeutics. (frontiersin.org)
  • This framework was assigned to be XII on discovery of VxXIIA , VxXIIB and VxXIIC 2006, which also had been used for conotoxins from the I superfamily (Brown et al. (conoserver.org)
  • Compared to elapid snake toxins, α-conotoxins are much smaller, usually 13-25 amino acids in length, and have only two disulfide bonds. (frontiersin.org)
  • 18. α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells. (nih.gov)
  • 19. Molecular Determinants Conferring the Stoichiometric-Dependent Activity of α-Conotoxins at the Human α9α10 Nicotinic Acetylcholine Receptor Subtype. (nih.gov)