OrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
ConotoxinsConus SnailMollusk VenomsSnailsNicotinic AntagonistsDisulfidesCystineNeurotoxinsAmino Acid SequenceSodium Channel BlockersMolecular Sequence DataReceptors, NicotinicPeptidesProtein FoldingXenopusSequence Alignment
Conotoxins
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)
Conus Snail
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.
Mollusk Venoms
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.
Snails
Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.
Nicotinic Antagonists
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.
Disulfides
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
Cystine
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.
Neurotoxins
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.
Amino Acid Sequence
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.
Sodium Channel Blockers
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.
Molecular Sequence Data
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.
Receptors, Nicotinic
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.
Peptides
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.
Protein Folding
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
Xenopus
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
Sequence Alignment
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)

Protein folding determinants: Structural features determining alternative disulfide pairing in α- and χ/λ-conotoxins |...
α-Conotoxins isolated from Conus venoms contain 11-19 residues and preferentially fold into the globular conformation that possesses a specific disulfide pairing pattern (C1-3, C2-4). We and others isolated a new family of χ-conotoxins (also called λ conotoxins) with the conserved cysteine framework of α-conotoxins but with alternative disulfide pairing (C1-4, C2-3) resulting in the ribbon conformation. In both families, disulfide pairing and hence folding are important for their biological potency. By comparing the structural differences, we identified potential structural determinants responsible for the folding tendencies of these conotoxins. We examined the role of conserved proline in the first intercysteine loop and the conserved C-terminal amide on folding patterns of synthetic analogues of ImI conotoxin by comparing the isoforms with the regiospecifically synthesized conformers. Deamidation at the C-terminus and substitution of proline in the first intercysteine loop switch the ...
https://scholarbank.nus.edu.sg/handle/10635/101476
Toxins | Free Full-Text | Cone Snails: A Big Store of Conotoxins for Novel Drug DiscoveryToxins | Free Full-Text | Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With
http://mdpi.com/2072-6651/9/12/397
Marine Drugs | Free Full-Text | ω-Conotoxins GVIA, MVIIA and CVID: SAR and Clinical Potential | HTMLMarine Drugs | Free Full-Text | ω-Conotoxins GVIA, MVIIA and CVID: SAR and Clinical Potential | HTML
Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
http://www.mdpi.com/1660-3397/4/3/193/htm
Analgesic conopeptides targeting G protein-coupled receptors reduce ex by Mahsa Sadeghi, Jeffrey R. McArthur et al.Analgesic conopeptides targeting G protein-coupled receptors reduce ex by Mahsa Sadeghi, Jeffrey R. McArthur et al.
Conotoxins (conopeptides) are a diverse group of peptides isolated from the venom of marine cone snails. Conus peptides modulate pain by interacting with voltage-gated ion channels and G protein-coupled receptors (GPCRs). Opiate drugs targeting GPCRs have long been used, nonetheless, many undesirable side effects associated with opiates have been observed including addiction. Consequently, alternative avenues to pain management are a largely unmet need. It has been shown that various voltage-gated calcium channels (VGCCs) respond to GPCR modulation. Thus, regulation of VGCCs by GPCRs has become a valuable alternative in the management of pain. In this review, we focus on analgesic conotoxins that exert their effects via GPCR-mediated inhibition of ion channels involved in nociception and pain transmission. Specifically, α-conotoxin Vc1.1 activation of GABAB receptors and inhibition of voltage-gated calcium channels as a novel mechanism for reducing the excitability of dorsal root ganglion neurons is
https://ro.uow.edu.au/ihmri/1148/
γ-Aminobutyric acid type B (GABAB) receptor expression is needed for i by Hartmut Cuny, Andrew de Faoite et al.γ-Aminobutyric acid type B (GABAB) receptor expression is needed for i by Hartmut Cuny, Andrew de Faoite et al.
α-Conotoxins Vc1.1 and RgIA are small peptides isolated from the venom of marine cone snails. They have effective anti-nociceptive actions in rat models of neuropathic pain. Pharmacological studies in rodent dorsal root ganglion (DRG) show their analgesic effect is mediated by inhibition of N-type (Cav2.2) calcium channels via a pathway involving γ-aminobutyric acid type B (GABAB) receptor. However, there is no direct demonstration that functional GABAB receptors are needed for inhibition of the Cav2.2 channel by analgesic α-conotoxins. This study examined the effect of the GABAB agonist baclofen and α-conotoxins Vc1.1 and RgIA on calcium channel currents after transient knockdown of the GABAB receptor using RNA interference. Isolated rat DRG neurons were transfected with small interfering RNAs (siRNA) targeting GABAB subunits R1 and R2. Efficient knockdown of GABAB receptor expression at mRNA and protein levels was confirmed by quantitative real time PCR (qRT-PCR) and immunocytochemical analysis,
http://ro.uow.edu.au/ihmri/613/
Dr Richard Clark - UQ ResearchersDr Richard Clark - UQ Researchers
Designing novel conotoxins with therapeutic potential Conotoxins, with their exquisite specificity and potency have recently created much excitement as drug leads for the treatment of chronic pain. For example, the conotoxin MVIIA (also known as Ziconotide or Prialt) has been approved for use in the U.S. and Europe for the treatment of pain and several other conotoxins have entered clinical trials. In addition, a number of conotoxins have played a critical role in dissecting the molecular mechanisms of ion channel and transporter functions in the nervous system.. There are projects available in the design of novel conotoxins that target specific receptors involved in pain.. ...
http://researchers.uq.edu.au/researcher/946
Sequence Similarity - 1G1P: NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus that Selectively Acts...Sequence Similarity - 1G1P: NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus that Selectively Acts...
1G1P: NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus That Selectively Acts on Vertebrate Neuronal Na+ Channels.
http://www.rcsb.org/pdb/explore/sequenceCluster.do?structureId=1G1P
Biodiversity helps medical research: Predatory Marine Snails - Speaking of ResearchBiodiversity helps medical research: Predatory Marine Snails - Speaking of Research
by Justin A. Varholick Ph.D., University of Florida, Department of Biology and UF Genetics Institute Too often we read about new research using mice, rats, non-human primates, and fish. These few categories of animals teach us a lot about biology and how we may intervene to cure or alleviate a human disease. But, what about…
https://speakingofresearch.com/2019/01/24/biodiversity-helps-medical-research-predatory-marine-snails/
Conotoxins Containing Nonnatural Backbone Spacers: Cladistic-Based Design, Chemical Synthesis, and Improved Analgesic ActivityConotoxins Containing Nonnatural Backbone Spacers: Cladistic-Based Design, Chemical Synthesis, and Improved Analgesic Activity
Disulfide-rich neurotoxins from venomous animals continue to provide compounds with therapeutic potential. Minimizing neurotoxins often results in removal of disulfide bridges or critical amino acids. To address this drug-design challenge, we explored the concept of disulfide-rich scaffolds consisting of isostere polymers and peptidic pharmacophores. Flexible spacers, such as amino-3-oxapentanoic or 6-aminohexanoic acids, were used to replace conformationally constrained parts of a three-disulfide-bridged conotoxin, SIIIA. The peptide-polymer hybrids, polytides, were designed based on cladistic identification of nonconserved loci in related peptides. After oxidative folding, the polytides appeared to be better inhibitors of sodium currents in dorsal root ganglia and sciatic nerves in mice. Moreover, the polytides appeared to be significantly more potent and longer-lasting analgesics in the inflammatory pain model in mice, when compared to SIIIA. The resulting polytides provide a promising ...
https://scholars.latrobe.edu.au/display/publication23550
RCSB PDB - 1M2C: THREE-DIMENSIONAL STRUCTURE OF ALPHA-CONOTOXIN MII, NMR, 14 STRUCTURESRCSB PDB - 1M2C: THREE-DIMENSIONAL STRUCTURE OF ALPHA-CONOTOXIN MII, NMR, 14 STRUCTURES
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
https://www.rcsb.org/structure/1M2C
TCDB » SEARCHTCDB » SEARCH
K+ channel of 529 aas and 6 TMSs, Kv1.6 or KCNA6. It can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members (). channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (Grupe et al. 1990). It is inhibited by 0.6 μM β-defensin 3 (BD3) (Zhang et al. 2018) as well as by neurotoxic cone snail peptide μ-GIIIA and other conotoxins (Leipold et al. 2017 ...
https://tcdb.org/search/result.php?tc=1.A.1.2.29
Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoproteinDegenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein
CONICET Digital, el repositorio institucional del CONICET, un servicio gratuito para acceder a la producción científico-tecnológica de investigadores, becarios y demás personal del CONICET.
https://ri.conicet.gov.ar/handle/11336/29271?show=full
Conotoxin | Tinnitus Talk Support ForumConotoxin | Tinnitus Talk Support Forum
http://onlinelibrary.wiley.com/doi/10.1002/anie.201000620/abstract The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain...
https://www.tinnitustalk.com/threads/conotoxin.7507/
Plus itPlus it
Voltage-gated Na+ channels are involved in the generation of action potentials in excitable cells. Structural determinants of major physiological characteristics (i.e., ion selectivity, gating, and ligand binding) are localized in the α subunit (Catterall, 2000; Hille, 2001). It is composed of four homologous domains (I-IV) quasi-symmetrically arranged around the central pore (Sato et al., 2001). Each domain contains six transmembrane segments (S1-S6), a pore-forming region (P), and the intracellular N and C ends (Guy and Seetharamulu, 1986; Denac et al., 2000). The P region contains the selectivity filter formed by a circular motif of highly conserved Asp, Glu, Lys, and Ala residues called the DEKA locus (Terlau et al., 1991; Heinemann et al., 1992). The selectivity filter separates the outer pore, which is targeted by tetrodotoxin (TTX), saxotoxin, and conotoxins, from the inner pore, which is targeted by local anesthetics (LAs) and other small cationic drugs (Zhorov and Tikhonov, 2004). Na+ ...
http://molpharm.aspetjournals.org/content/74/4/1033
Red Glial Iberoamericana (RGIA) | Bernardo Castellano
Raffaella G., Sole,C., Llecha,N, Segura, M.F., Moubarak,R., Iglesias-Guimarais,V., Perez-Garcia,M.J., Reix,S., Zhang,J., Badiola,N., Sanchis,D., Rodriguez-Alvarez,J.,Trullas,R., Yuste,V.J., and J.X. Comella ...
http://rgia.com.es/paises/mostra_grups.php?id=84
Red Glial Iberoamericana (RGIA) | Bernardo Castellano
Analizar y valorar, en la rata como modelo animal de neurodegeneración, posibles mecanismos inflamatorios involucrados en la toxicidad del péptido Aβ. Así como mecanismos por los que el calcio participa en la activación de astrocitos en fases tempranas (24h - 2 semanas) de la toxicidad inducida por el péptido Aβ1-42. ...
http://rgia.com.es/paises/mostra_grups.php?id=72
Site-ul oficial al pictorului Vasile Traistariu
Am vazut emisiunea lui Maruta si sunt impresionata de evolutia voastra, a fratilor Traistariu! Sunteti cu totii niste artisti, fiecare in arta lui. Parintii vostri de acolo de unde sunt, va lumineaza drumul cu dragoste si cu siguranta sunt mandrii ca voi sunteti cu totii si fiecare in parte niste copii atat de minunati. Imi plac tablourile tale Vasile, dar nu imi este clar cum pot sa le cumpar?! Imi plac absolut toate, si imi doresc sa imi impodobesc micuta mea casa cu cateva dintre ele...caci simt energia lor benefica...Astept un semn in acest sens pe adresa mea de email pe care am lasat-o. Dumnezeu sa va ocroteasca sa fiti cu sufletul mereu impreuna...viata asta materiala, vine si pleaca...voi existati prin simtul vostru artistic. Va doresc din tot sufletul sa fiti de sfintele sarbatori de Paste impreuna asa cum imi doresc si pentru familia mea (eu am trei copii minunati si extraordinari ca si voi) si pentru toti cei care pe lumea asta inteleg ca ne-am nascut sa ne iubim neconditionat ...
http://www.vasiletraistariu.ro/Cartea-de-oaspeti.php?pageID=2
Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIA - ResearchOnline@JCUAllosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIA - [email protected]
A peptide contained in the venom of the predatory marine snail Conus tulipa, rho-TIA, has previously been shown to possess alpha1-adrenoreceptor antagonist activity. Here, we further characterize its pharmacological activity as well as its structure-activity relationships. In the isolated rat vas deferens, rho-TIA inhibited alpha1-adrenoreceptor-mediated increases in cytosolic Ca2+ concentration that were triggered by norepinephrine, but did not affect presynaptic alpha2-adrenoreceptor-mediated responses. In radioligand binding assays using [125I]HEAT, rho-TIA displayed slightly greater potency at the alpha 1B than at the alpha 1A or alpha 1D subtypes. Moreover, although it did not affect the rate of association for [3H]prazosin binding to the alpha 1B-adrenoreceptor, the dissociation rate was increased, indicating non-competitive antagonism by rho-TIA. N-terminally truncated analogs of rho-TIA were less active than the full-length peptide, with a large decline in activity observed upon removal ...
https://researchonline.jcu.edu.au/273/
Apple Academic PressApple Academic Press
Marine snails form the dominant component of molluscan faunas throughout the worlds oceans. There are about 600 different species of cone snails found distributed in warm and tropical seas and oceans worldwide, and the greatest diversity is seen in the Western Indo-Pacific Region. Cone snail venoms such as conotoxins and conopeptides show great promise as a source of new and medically important substances. The synthetic version of the conopeptide called ziconotide has been approved as a medication in the United States by the FDA (Food and Drug Administration) and is in current use as an analgesic (pain reliever). Conantokins, which are a family of conopeptides found in cone snail venom, serve as sleeper peptides, and these peptides work by a mechanism that may be helpful for people with epilepsy ...
http://appleacademicpress.com/biology-and-ecology-of-venomous-marine-snails-/9781771883306
ConoServerConoServer
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. 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. For any other use please contact David Craik ([email protected]). ...
http://conoserver.org/?page=card&table=structure&id=192
ConoServerConoServer
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. 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. For any other use please contact David Craik ([email protected]). ...
http://conoserver.org/?page=card&table=protein&id=3908
In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds | Journal of Venomous Animals...In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds | Journal of Venomous Animals...
During evolution, nature has embraced different strategies for species to survive. One strategy, applied by predators as diverse as snakes, scorpions, sea anemones and cone snails, is using venom to immobilize or kill a prey. This venom offers a unique and extensive source of chemical diversity as it is driven by the evolutionary pressure to improve prey capture and/or to protect their species. Cone snail venom is an example of the remarkable diversity in pharmacologically active small peptides that venoms can consist of. These venom peptides, called conopeptides, are classified into two main groups based on the number of cysteine residues, namely disulfide-rich and disulfide-poor conopeptides. Since disulfide-poor conotoxins are minor components of this venom cocktail, the number of identified peptides and the characterization of these peptides is far outclassed by its cysteine-rich equivalents. This review provides an overview of 12 families of disulfide-poor peptides identified to date as well as the
https://jvat.biomedcentral.com/articles/10.1186/s40409-016-0083-6/tables/3
New medicines at risk from biodiversity lossNew medicines at risk from biodiversity loss
With more than 2600 studies published in the last 20 years, there is much excitement about conotoxins in biomedicine. Most conotoxins are a succinct ten to forty amino acids in length and are exquisitely selective about their receptor binding sites. This makes them powerful tools for understanding how cells work and a rich source for discovery of new medicines, said Bernstein. Among many discoveries, conotoxins that block key neurological pathways have been effective in the early detection and may also help treat small-cell lung cancer, one of the most devastating human cancers. A compound now in clinical trials has powerful anti-epileptic activity. Experiments suggest that conotoxins could treat muscle spasticity following spinal cord injury. They could prevent cell death when there is inadequate circulation, such as during strokes, head injuries or coronary bypass surgery. They could also be used to treat clinical depression, heart arrhythmias and urinary incontinence ...
http://www.innovations-report.com/html/reports/environment-sciences/report-22538.html
Evolution of Conus peptide toxins: analysis of Conus californicus Reeve, 1844.Evolution of Conus peptide toxins: analysis of Conus californicus Reeve, 1844.
Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E., Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S., Olivera B.M.. Conus species are characterized by their hyperdiverse toxins, encoded by a few gene superfamilies. Our phylogenies of the genus, based on mitochondrial genes, confirm previous results that C. californicus is highly divergent from all other species. Genetic and biochemical analysis of their venom peptides comprise the fifteen most abundant conopeptides and over 50 mature cDNA transcripts from the venom duct. Although C. californicus venom retains many of the general properties of other Conus species, they share only half of the toxin gene superfamilies found in other Conus species. Thus, in these two lineages, approximately half of the rapidly diversifying gene superfamilies originated after an early Tertiary split. Such results demonstrate that, unlike endogenously acting gene families, these genes are likely to be significantly more ...
https://www.uniprot.org/citations/20363338
Taxonomic Classification of the Cone Shell Snail (Conus Geographus) and the uses of its venom - WriteWorkTaxonomic Classification of the Cone Shell Snail (Conus Geographus) and the uses of its venom - WriteWork
Conus geographus�Intro - Slide 1 (Cone shell snail)Ralph Waldo Emerson once stated The most dangerous thing is illusion. Good morning/afternoon ladies and gentlemen, my name is Tobias and today I will speak to you on the dangerous illusion tha...
http://www.writework.com/essay/taxonomic-classification-cone-shell-snail-conus-geographus
VAPAGuide - Biomedical database - Miscellaneous animals - Conus spp.
Cone shells (Conidae) are a group of predatory marine snails. This group has not yet been divided into various genera, so that all of the approximately 300 species are included in the genus Conus.. Cone shells, like their close relatives the Turrids (Turridae), Mitre shells (Mitridae), Cytharidae and Auger shells (Terebridae), have developed an unusual venom apparatus for catching prey. However, only Cone shells are known to have caused envenoming in humans.. The shell of the Conidae is in the form of a rolled cone. There is a slit-like opening on the long side through which the animals evert their foot. The larger species, such as C. geographus, reach a length of up to 15 cm. With their often strikingly beautifully patterned shells, Cone shells are highly prized among shell collectors.. Cone shells live in shallow water, including coastal zones, especially reef areas, where they conceal themselves in crevices or bury themselves in the sand during the day. Only at dusk do they start appearing ...
http://vapaguide.info/catalogue/MIS-70
Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were conantokin-G structure-based designed | BMC...Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were conantokin-G structure-based designed | BMC...
The GluN2B subunit of the N-methyl-d-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit. In this study we tested this prediction for two of these peptides EAR16 and EAR18. The effects of EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and EAR18 reduced the NMDA
https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-017-0361-4
Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR: structure and identification of key receptor-binding...Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR: structure and identification of key receptor-binding...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
https://www.ncbi.nlm.nih.gov/pubmed/18295795?dopt=Abstract
Alpha-conotoxin-like MIB - Conus magus (Magus cone)Alpha-conotoxin-like MIB - Conus magus (Magus cone)
Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
https://www.uniprot.org/uniprot/P0C1W2
Identification of residues in the neuronal α<sub>7</sub> acetylcholine receptor that confer selectivity for...
TY - JOUR. T1 - Identification of residues in the neuronal α7 acetylcholine receptor that confer selectivity for conotoxin ImI. AU - Quiram, Polly A.. AU - Sine, Steven M.. PY - 1998/5/1. Y1 - 1998/5/1. N2 - To identify residues in the neuronal α7 acetylcholine subunit that confer high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we constructed α7-α1 chimeras containing segments of the muscle α1 subunit inserted into equivalent positions of the neuronal α7 subunit. To achieve high expression in 293 human embryonic kidney cells and formation of homo-oligomers, we joined the extracellular domains of each chimera to the M1 junction of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to the chimeric receptors reveal three pairs of residues in equivalent positions of the primary sequence that confer high affinity of CTx ImI for α7/5HT-3 over α1/5HT-3 homo-oligomers. Two of these pairs, α7Trp55/α1Arg55 and α7Ser59/α1Gln59, are within one of ...
https://mayoclinic.pure.elsevier.com/en/publications/identification-of-residues-in-the-neuronal-%CE%B1sub7sub-acetylcholine
Kalins Lunker GrubsKalins Lunker Grubs
The tradition continues with Kalins Lunker Grub. Precise, proven design provides Maximum Action at Ultra-Slow Speed, the hallmark of all Kalin baits.
http://www.landbigfish.com/Kalins/Kalins-Lunker-Grubs
imi place sa plang. | Embrionus uterusimi place sa plang. | Embrionus uterus
imi place sa plang. imi face buzele mai mari. am cearcane. asta inseamna ca ele au luat o parte din ochii mei. nori de cenusa. ma destram. dar imi place. imi place sa plang. ceva imi apasa inima. or fi lacrimi? tip: aaaaaaaaaaaaaaaaaaa! pot sa fac asta. sau nu. imi place sa plang.
https://embrionu.wordpress.com/2010/06/09/imi-place-sa-plang/
imi:calificari profesionale:notificari:moase [IMI PQ NET România]imi:calificari profesionale:notificari:moase [IMI PQ NET România]
Notificări IMI referitoare la formarea pentru moașe Coordonator notificări: Centrul Național de Recunoaștere și Echivalare a Diplomelor Autoritate competentă: Ordinul Asistenţilor Medicali Generalişti, Moaşelor şi Asistenţilor Medicali din România Notificări primite |datatables page-length=„10
https://cnred.edu.ro/imipqnet/doku.php?id=imi:calificari_profesionale:notificari:moase&ns=imi%3Acalificari_profesionale%3Acardul_profesional_european&tab_files=files&do=media
IMI Delivers Resilient ResultsIMI Delivers Resilient Results
LONDON -- IMI , the global engineering company that specializes in the precise control and movement of fluids in critical applications, rose 8% on the week following publication of its preliminary results for the full year ended Dec. 31. The
https://www.aol.com/2013/03/09/imi-delivers-resilient-results/
The scale of the funding enables real impact | IMI Innovative Medicines...The scale of the funding enables real impact | IMI Innovative Medicines...
The Childrens Tumor Foundation is one of IMIs Associated Partners. Annette Bakker, the Foundations president, says that the unique IMI model ensures alignment between industry and public partners.
https://www.imi.europa.eu/news-events/newsroom/scale-funding-enables-real-impact
Ağıllı elektronikaAğıllı elektronika
Ağıllı elektronika - Geniş seçimi, malların aşağı qiymət, keyfiyyət zəmanəti. Gəlin və seçin. Mağazamız sizi gözləyir.
http://www.gettherefast.org/agilli-elektronika/
Vesicular Monoamine Transporters | Involvement of p53 in the cytotoxic activity of the NAMPT inhibitor FK866Vesicular Monoamine Transporters | Involvement of p53 in the cytotoxic activity of the NAMPT inhibitor FK866
The Conus genus includes around 500 species of marine mollusks using a peculiar production of venomous peptides referred to as conotoxins (CTX). S1) living generally in the tropical marine areas. About 700 species of Cone snails express hundreds of peptide toxins collectively known as conotoxins (CTX) aimed to self-defense, competition and predation of other marine species by means of stingCstructures that were reported to be fatal for human since from 300 years ago. CTX, however, do not exert only venomous activity but have a lot of pharmacological properties with specific bioactivity in the treatment of neurological disorders and the associated pain belief [1,2,3]. The presence of disulfide bonds is the important characteristic for natural function of CTX that enable to separate CTX into two primary types, the disulfide-rich peptides and no-disulfide-rich types; the foremost is generally composed of no more than 30 proteins and the next contains as much as 80 proteins. CTX are grouped into ...
http://fk866.net/category/vesicular-monoamine-transporters/
Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and TPowerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T
Subunit non-selective N-methyl-D-aspartate (NMDA) receptor antagonists reduce injury-induced pain behavior, but generally produce unacceptable side effects. In this study, we examined the antinociceptive and motor effects of cone snail venom-derived peptides, conantokins G and T (conG and conT), whi …
https://pubmed.ncbi.nlm.nih.gov/12507705/?dopt=Abstract
Cone Snail Venom Facts and Potential Medical Benefits - Owlcation - EducationCone Snail Venom Facts and Potential Medical Benefits - Owlcation - Education
Cone snails use their venom to paralyze their prey. Although the venom is often dangerous for humans, it contains chemicals that may have important medical benefits.
https://owlcation.com/stem/Cone-Snails-Dangerous-Venom-With-Medicinal-Uses
Scientist identifies cone snails strike as one of the quickest in the animal kingdomScientist identifies cone snails strike as one of the quickest in the animal kingdom
With the use of ultra-high-speed videography, Ecology and Evolutionary Biology Associate Professor Emanuel Azizi and colleagues from Occidental College Los Angeles have shed light on the hunting mechanism of the cone snail Conus catus. Published online in Current Biology - Cell Press, the researchers identified the snails hydraulically propelled feeding structure as the quickest movement among mollusks by an order of magnitude.
https://phys.org/news/2019-08-scientist-cone-snail-quickest-animal.html
Cone SnailCone Snail
But beware! Cone Snails have a extremely potent toxin (called Conotoxin), and they have to. They are tiny little guys who dont move very fast. Their toxin needs to paralyze their prey quickly, otherwise itll get away. The toxin in these Snails has the ability to kill a human being, and there is no known antivenom. They attack via a barb that shoots out from their shell, and the type of paralysis is dependent on the species. When their prey is immobilized, they draw it back in to their shell, still attached to the barb. Cone Snails are carnivorous and predatory, and feed off of fish, worms, and other mollusks, depending on the specific species ...
http://animaladay.blogspot.com/2010/11/cone-snail.html
Gelatinous Marine Snail: Tiny Marine Snails Fly in Water Like Winged Insects [VIDEO] : News : Nature World NewsGelatinous Marine Snail: Tiny Marine Snails Fly in Water Like Winged Insects [VIDEO] : News : Nature World News
Tiny marine snails known as sea butterflies appear to fly underwater much like winged insects do when taking to the sky - representsing a remarkable example of convergent evolution, where two unrelated species develop features that are used in similar ways.
http://www.natureworldnews.com/articles/20053/20160219/sea-butterfly-tiny-marine-snails-fly-underwater-winged-insects-video.htm
Cone snail venom holds promise for medical treatments for cancer and addiction | EurekAlert! Science NewsCone snail venom holds promise for medical treatments for cancer and addiction | EurekAlert! Science News
While considered a delicacy in some parts of the world, snails have found a more intriguing use to scientists and the medical profession offering a plethora of research possibilities.
https://www.eurekalert.org/pub_releases/2015-01/fau-csv011315.php
Chino CabaltejaChino Cabalteja
Research Interests:. Foldamers are unnatural oligomers with a propensity to adopt well-defined conformations. These molecules have seen success in the mimicry of canonical peptide secondary structures such as -helices and -sheets. Current efforts in the field involve the application of foldamer design strategies to mimic higher-order protein structures and novel peptide architectures. Disulfide-rich peptides are notable candidates for foldamer research due to their intricate folding patterns and potent bioactivities. I am interested in establishing foldamer design principles for the synthesis of disulfide-rich peptide analogs with heterogeneous backbone modifications that manifest specific conformations, desired functionality and improved pharmacological properties.. Education:. B.S. in Microbiology, University of Hawaii at Manoa, 2008. M.S. in Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 2014. ...
http://mbsb.pitt.edu/index.php/site-map/articles/85-students/222-chino-cabalteja
Pain relief from the sea | Stories of Australian SciencePain relief from the sea | Stories of Australian Science
The big problems with morphine are addictiveness and the fact that people develop a tolerance to it, says Professor David Adams, director of the RMIT Health Innovations Research Institute. With the painkillers derived from cone snail venom, we dont have those problems. People dont develop tolerance, and they dont get hooked.. Also, theres a wide safety margin. With morphine, theres little room for error. If you overdose, youre likely to die. But with the venom peptides, there may be side-effects but you will survive.. David leads research into the cocktail of peptides-fragments of protein-with which the cone snail paralyses its prey. These peptides have exquisite selectivity for their molecular targets, he says. So his team is geared to developing new treatments for chronic nerve-based pain by discovering and purifying peptides that target particular pain receptors.. Worldwide, there are more than 700 species of cone snails, about two-thirds of which are found in the Great Barrier ...
http://stories.scienceinpublic.com.au/2011/coneforpainrelief/
Harnessing The Reactivity Of The N-Methyl Diaminobenzoyl Linker To Access C-Terminall . . . by Christine ArbourHarnessing The Reactivity Of The N-Methyl Diaminobenzoyl Linker To Access C-Terminall . . . by Christine Arbour
This thesis describes the exploration of accessing C-terminally modified and macrocyclic peptides through N-acyl urea (MeNbz) displacement. Prior to this work, the diaminobenzoyl linker was used to access thioesters for native chemical ligation. Only solution-phase displacement of the N-acyl urea with thiol nucleophiles was previously reported. The N-Me-diaminobenzoyl (MeDbz) linker was initially used to access C-terminal glycine esters, amides, and acids from a single peptide substrate. This led to the total synthesis of Conopressin G and two analogs. The propensity of the C-terminal cysteine residue to undergo epimerization was investigated using this strategy. After optimization, C-terminal cysteine esters, amides, and acids were prepared with no detectible epimerization. This strategy was used toward the total synthesis of alpha-Conotoxin ImI. In addition, amino acids were used as nucleophiles to elongate the C terminus of the peptide, circumventing tedious solid-phase peptide syntheses. Lastly, an
https://digitalcommons.wayne.edu/oa_dissertations/2141/
The Single Disulfide-Directed β-Hairpin Fold. Dynamics, Stability, and Engineering<...
TY - JOUR. T1 - The Single Disulfide-Directed β-Hairpin Fold. Dynamics, Stability, and Engineering. AU - Chittoor, Balasubramanyam. AU - Krishnarjuna, Bankala. AU - Morales, Rodrigo A.V.. AU - Macraild, Christopher A.. AU - Sadek, Maiada M.. AU - Leung, Eleanor W.W.. AU - Robinson, Samuel D.. AU - Pennington, Michael William. AU - Norton, Raymond S.. PY - 2017/5/16. Y1 - 2017/5/16. N2 - Grafting bioactive peptide sequences onto small cysteine-rich scaffolds is a promising strategy for enhancing their stability and value as novel peptide-based therapeutics. However, correctly folded disulfide-rich peptides can be challenging to produce by either recombinant or synthetic means. The single disulfide-directed β-hairpin (SDH) fold, first observed in contryphan-Vc1, provides a potential alternative to complex disulfide-rich scaffolds. We have undertaken recombinant production of full-length contryphan-Vc1 (rCon-Vc1[Z1Q]) and a truncated analogue (rCon-Vc11-22[Z1Q]), analyzed the backbone dynamics of ...
https://research.monash.edu/en/publications/the-single-disulfide-directed-%CE%B2-hairpin-fold-dynamics-stability-a
Coniine
Coniine,(2S)-2-Propylpiperidine,cicutine,conicine,Hydrobromide,Coniine Hydrobromide,Hydrochloride,Coniine Hydrochloride,(R)-(-)-Form,(R)-(-)-Coniine,(+/-)-Form,(+/-)-Coniine
http://www.druglead.com/cds/Coniine.html
Publications by: Paramjit S. Bansal Also publishes as (Paramjit Bansal, P. Bansal) - ResearchOnline@JCUPublications by: Paramjit S. Bansal Also publishes as (Paramjit Bansal, P. Bansal) - [email protected]
Wilson, David, Bansal, Paramjit S., Carter, David A., Vetter, Irina, Nicke, Annette, Dutertre, Sébastien, and Daly, Norelle (2020) Characterisation of a novel A-superfamily conotoxin. Biomedicines, 8 (5). 128. Takjoo, Rozita, Wilson, David T., Bansal, Paramjit, Loukas, Alex, Smout, Michael J., and Daly, Norelle L. (2020) Folding of truncated granulin peptides. Biomolecules, 10 (8). 1152. Schmidt, Casey A., Wilson, David T., Cooke, Ira, Potriquet, Jeremy, Tungatt, Katie, Muruganandah, Visai, Boote, Chloe, Kuek, Felicity, Miles, John J., Kupz, Andreas, Ryan, Stephanie, Loukas, Alex, Bansal, Paramjit S., Takjoo, Rozita, Miller, David J., Peigneur, Steve, Tytgat, Jan, and Daly, Norelle (2020) Identification and characterization of a peptide from the stony coral Heliofungia actiniformis. Journal of Natural Products, 83 (11). pp. 3454-3463. Dastpeyman, Mohadeseh, Giacomin, Paul, Wilson, David, Nolan, Matthew J., Bansal, Paramjit S., and Daly, Norelle L. (2019) A C-terminal fragment of chlorotoxin ...
https://researchonline.jcu.edu.au/view/jcu/6CD5B344ACF420DB66BD9C313B16235F.html
Cyclic analogues of α-conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal...Cyclic analogues of α-conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal...
Castro J, Grundy L, Deiteren A, Harrington AM, ODonnell T, Maddern J, Moore J, Garcia-Caraballo S, Rychkov GY, Yu R, Kaas Q, Craik DJ, Adams DJ, Brierley ...
https://www.painresearchforum.org/papers/89469-cyclic-analogues-conotoxin-vc11-inhibit-colonic-nociceptors-and-provide-analgesia-mouse
CONANTOKIN (PS60025) | InterPro | EMBL-EBICONANTOKIN (PS60025) | InterPro | EMBL-EBI
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
http://www.ebi.ac.uk/interpro/signature/PS60025
IMI 2 Open Info Day 2014 | IMI - Innovative Medicines InitiativeIMI 2 Open Info Day 2014 | IMI - Innovative Medicines Initiative
IMI held its IMI 2 Open Info Day in Brussels on Tuesday 30 September 2014. The event was well-attended, with more than 290 people participating either in person or remotely via the webcast. On top of a review of the new IMI 2 rules and Call procedures, IMIs founding partners presented their perspectives on IMI 2. In the afternoon, there were two topic-related workshops on the IMI 2 Call 1 topics, as well as plenty of networking opportunities throughout the day. During the workshops, participants were invited to make an elevator pitch or short presentation to the other participants about their organisation. The final session gave a preview of whats coming later this year in IMIs second IMI 2 Call, giving participants the chance to ask three of the topic writers directly about the new indicative topics.. The whole days events were recorded and the videos of each session will be viewable on IMIs YouTube channel.. ...
http://www.imi.europa.eu/news-events/events/imi-2-open-info-day-2014
Doomstermaniac
The first Part is atmospheric, dense and more progressive. The second part (my favorite) is also atmospheric, dense with some guttural vocals and painful chants, and the best ultra-slow riffs, sometimes almost Funeral Doom (anybody says Evoken ...
http://doomstermaniac.blogspot.com.br
Coniine | The Merck Index Online
The Merck Index* Online | Coniine | Monograph containing literature references, physical and biological properties and relevant information
https://www.rsc.org/Merck-Index/monograph/m3759/coniine?q=unauthorize
calificari profesionale [IMI PQ NET România]calificari profesionale [IMI PQ NET România]
Autorităţile competente pentru Calificări Profesionale ID Denumire neoficială Denumiri Ţara Region Town E-mail Telephone 1587 Departamentul pentru evaluarea şi recunoaşterea diplomelor din învăţământ Regierungspräsidium Tübingen Abt.7 -Schule und Bildung- Ref.73 Germania Baden-Württemberg Tübingen [email protected] 7071- 200 0 1178 ASOCIAŢIA GREACĂ A MEDICILOR ΠΑΝΕΛΛΗΝΙΟΣ ΙΑΤΡΙΚΟΣ ΣΥΛΛΟΓΟΣ Grecia null ΑΘΗΝΑ [email protected] 2107258660 8365 Academia de management, Școala de …
https://www.cnred.edu.ro/imipqnet/doku.php?id=calificari_profesionale&bootswatch-theme=paper
calificari profesionale [IMI PQ NET România]calificari profesionale [IMI PQ NET România]
Autorităţile competente pentru Calificări Profesionale ID Denumire neoficială Denumiri Ţara Region Town E-mail Telephone 1587 Departamentul pentru evaluarea şi recunoaşterea diplomelor din învăţământ Regierungspräsidium Tübingen Abt.7 -Schule und Bildung- Ref.73 Germania Baden-Württemberg Tübingen [email protected] 7071- 200 0 1178 ASOCIAŢIA GREACĂ A MEDICILOR ΠΑΝΕΛΛΗΝΙΟΣ ΙΑΤΡΙΚΟΣ ΣΥΛΛΟΓΟΣ Grecia null ΑΘΗΝΑ [email protected] 2107258660 8365 Academia de management, Școala de …
https://cnred.edu.ro/imipqnet/doku.php?id=calificari_profesionale&bootswatch-theme=default
BeautyBarometer, cine, ce, cum, CONCURS - BeautyBarometerBeautyBarometer, cine, ce, cum, CONCURS - BeautyBarometer
Premiul va rasplati descrierea care ma va convinge si pe mine ca imi cunosti blogul. Atentie nu trebuie nici sa ma lauzi, nici sa ma faci praf, eu nu sunt fana a extremelor, adica daca imi citesti blogul te-ai cam lamurit despre ce scriu si cum scriu. Imi doresc sa imi spui simplu si in termeni normali ce reprezinta blogul meu pentru tine si cum i-ai spune tu rapid cuiva ceva despre blogul meu. Lasa-mi textul acesta in comentariu la acest articol. ...
https://beautybarometer.com/beautybarometer-cine-ce-cum-concurs/
CRAFT-alnica: TOP3 209. izzivaCRAFT-alnica: TOP3 209. izziva
Fotografijo izdelka objavite na svojem blogu, z direktno povezavo nazaj na CRAFT-alnico, zapisano v vaši objavi. Vaš URL naslov (povezava do objave izdelka in ne do bloga!) kopirajte in vstavite v InLinkz (modri gumbek na dnu objave) skupaj z vašimi imenom in e-mailom. ...
https://craft-alnica.blogspot.com/2018/05/top3-209-izziva.html?showComment=1526408078973
Procollagen-proline dioxygenaseProcollagen-proline dioxygenase
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 ...
https://en.wikipedia.org/wiki/Procollagen-proline_dioxygenase
CNF-Sr3CNF-Sr3
All conorfamides are disulfide-poor conotoxins. CNF-Sr3 shares 73.3% sequence similarity with CNF-Sr1 and 31.0% sequence ...
https://en.wikipedia.org/wiki/CNF-Sr3
NeurotoxinNeurotoxin
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 ...
https://en.wikipedia.org/wiki/Neurotoxin
Cone snailCone snail
The conotoxins contain target specificity and short sequences. An example of this phenomenon is ω-MVIIA which targets Ca2+ ... Gao B, Peng C, Yang J, Yi Y, Zhang J, Shi Q (December 2017). "Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery ... The toxins in these various venoms are called conotoxins. These are various peptides, each targeting a specific nerve channel ... Natural History Museum Rotterdam - photos of Conus shells Cone snail and conotoxins page The Conus Biodiversity website ...
https://en.wikipedia.org/wiki/Cone_snail
ConoServerConoServer
These toxins are known as conotoxins or conopeptides. The toxins are of importance to medical research. A notable feature of ...
https://en.wikipedia.org/wiki/ConoServer
Conus magusConus magus
Their venom contains conotoxins which have powerful neurotoxic effects. Given that they are capable of "stinging" humans, live ...
https://en.wikipedia.org/wiki/Conus_magus
Vitamin KVitamin K
Buczek O, Bulaj G, Olivera BM (December 2005). "Conotoxins and the posttranslational modification of secreted gene products". ...
https://en.wikipedia.org/wiki/Vitamin_K
ConotoxinConotoxin
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 ...
https://en.wikipedia.org/wiki/Conotoxin
P-type calcium channelP-type calcium channel
ω-Conotoxins are derived from the venom of cone snails. ω-Conotoxin MVIIC acts within the hippocampal CA1 pyramidal neurons to ...
https://en.wikipedia.org/wiki/P-type_calcium_channel
CapnelleneCapnellene
"Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
https://en.wikipedia.org/wiki/Capnellene
Conus victoriaeConus victoriae
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 ...
https://en.wikipedia.org/wiki/Conus_victoriae
TetrodotoxinTetrodotoxin
... neosaxitoxin and several of the conotoxins also bind the same site. The use of this toxin as a biochemical probe has elucidated ...
https://en.wikipedia.org/wiki/Tetrodotoxin
HydroxyprolineHydroxyproline
Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences. Hydroxylation of proline has been ...
https://en.wikipedia.org/wiki/Hydroxyproline
Mandë HolfordMandë Holford
Biodiversity-Derived Discovery of Novel Sodium Channel Blocking Conotoxins from Conus bullatus". Toxicon. 53 (1): 90-8. doi: ...
https://en.wikipedia.org/wiki/Mandë_Holford
CACNA1BCACNA1B
"The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels". The ...
https://en.wikipedia.org/wiki/CACNA1B
Baldomero OliveraBaldomero Olivera
These molecules, called conotoxins, led to a breakthrough in the study of ion channels and neuromuscular synapses. He ... His impressive research on both DNA biophysics and conotoxins has enabled Dr Olivera to serve as an editorial board member of ...
https://en.wikipedia.org/wiki/Baldomero_Olivera
HuwentoxinHuwentoxin
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 ...
https://en.wikipedia.org/wiki/Huwentoxin
Tropidolaemus wagleriTropidolaemus wagleri
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 ...
https://en.wikipedia.org/wiki/Tropidolaemus_wagleri
N-type calcium channelN-type calcium channel
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- ...
https://en.wikipedia.org/wiki/N-type_calcium_channel
Lourdes J. CruzLourdes J. Cruz
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 ...
https://en.wikipedia.org/wiki/Lourdes_J._Cruz
Ptu1Ptu1
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 ...
https://en.wikipedia.org/wiki/Ptu1
ConantokinConantokin
... s typically lack disulfide bonds, in contrast to most families of conotoxins, which have an unusually high density of ...
https://en.wikipedia.org/wiki/Conantokin
Insect toxinInsect toxin
They are relatively homologous to the calcium channel blockers omega-conotoxins from marine cone snails and belong to the four- ...
https://en.wikipedia.org/wiki/Insect_toxin
DKK-Sp1DKK-Sp1
... is also functionally similar to delta-conotoxins, which binds to the receptor site 6 of voltage-gated sodium channel, ...
https://en.wikipedia.org/wiki/DKK-Sp1
Conus regiusConus regius
C. regius is known to have more different conotoxins than any other Cone sail species, its conotoxin it's potentially of ...
https://en.wikipedia.org/wiki/Conus_regius
MolluscivoreMolluscivore
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 ...
https://en.wikipedia.org/wiki/Molluscivore
ConasprelloidesConasprelloides
Zugasti-Cruz, A., Aguilar, M.B., Falcon, A., Olivera, B.M., & Heimer de la Cotera, E.P. (2008) Two new 4-cys conotoxins ( ...
https://en.wikipedia.org/wiki/Conasprelloides
2010 in the Philippines2010 in the Philippines
Cruz is recognized as one of the five laureates of L'Oreal-UNESCO Awards for Women in Science for the discovery of conotoxins ...
https://en.wikipedia.org/wiki/2010_in_the_Philippines
Covalitoxin-IICovalitoxin-II
... knot motif that is formed by the cysteine residues shows analogy to other spider toxins and can also be found in ω-conotoxins, ...
https://en.wikipedia.org/wiki/Covalitoxin-II
List of MeSH codes (D20)List of MeSH codes (D20)
... conotoxins MeSH D20.888.590.162.720 - omega-conotoxins MeSH D20.888.590.162.720.700 - omega-conotoxin gvia MeSH D20.888.590.325 ...
https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D20)
SCOP 1.67: Superfamily j.30.1: ConotoxinsSCOP 1.67: Superfamily j.30.1: Conotoxins
More info for Superfamily j.30.1: Conotoxins. Timeline for Superfamily j.30.1: Conotoxins: *Superfamily j.30.1: Conotoxins ... Fold j.30: Conotoxins [58464] (1 superfamily). disulfide-rich fold. *. Superfamily j.30.1: Conotoxins [58465] (7 families) all ... Superfamily j.30.1: Conotoxins appears in SCOP 1.65. *Superfamily j.30.1: Conotoxins appears in SCOP 1.69. *Superfamily j.30.1 ... Lineage for Superfamily j.30.1: Conotoxins. *Root: SCOP 1.67 *. Class j: Peptides [58231] (111 folds). ...
http://scop.berkeley.edu/sunid=58465&ver=1.67
Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channelsAnalgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channels
Conotoxins (conopeptides) are small disulfide bonded peptides from the venom of marine cone snails. These peptides target a ... Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors ( ... Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channels Br J Pharmacol. ... Surprisingly, however, α-conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA(B) GPCR ...
https://pubmed.ncbi.nlm.nih.gov/22091786/?dopt=Abstract
Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins. | Pain Research ForumIdentification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins. | Pain Research Forum
Home , Papers , Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins. ... Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins.. ... Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins. ...
https://www.painresearchforum.org/papers/211857-identification-sensory-neuron-cav23-inhibitor-within-new-superfamily-macro-conotoxins
Conotoxins | Andrea Robinson GroupConotoxins | Andrea Robinson Group
Posted in Conotoxins, Dicarba peptides, Metathesis, Publications, Publications 2013 , Leave a comment ... Category Archives: Conotoxins. α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia. Posted ... Abstract Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides ...
https://andrearobinsongroup.com/category/conotoxins/
Medical Waste | Background | Environmental Guidelines | Guidelines Library | Infection Control | CDCMedical Waste | Background | Environmental Guidelines | Guidelines Library | Infection Control | CDC
Abrin; conotoxins; diacetoxyscirpenol; ricin; saxitoxin; Shiga-like ribosome inactivating proteins; tetrodotoxin Exclusions: ¶ ... 100 mg of conotoxins; 1,000 mg of diacetoxyscirpenol; 100 mg of ricin; 100 mg of saxitoxin; 100 mg of Shiga-like ribosome ...
https://www.cdc.gov/infectioncontrol/guidelines/environmental/background/medical-waste.html
Conotoxins: peptide toxins from cone snailsConotoxins: peptide toxins from cone snails
κ-conotoxins. κ-conotoxins target potassium channels and may result in enhanced neuronal excitability. Few κ-conotoxins such as ... ω-conotoxins. ω-conotoxins are potent inhibitors of N-type voltage-dependent calcium channels (VDCC) [8]. ω-conotoxin MVIIA, ... α-conotoxins. cash advance indianapolis. α-conotoxins are nicotinic acetylcholine receptor (nAChR) antagonists located in ... µ-conotoxins. μ-conotoxins target voltage-dependent sodium channels (Nav) preferentially in excitable cells of skeletal muscle ...
https://www.smartox-biotech.com/conotoxins-peptide-toxins
Primary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brainPrimary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brain
omega-Conotoxins* Substances * Calcium Channel Blockers * Calcium Channels * Peptides, Cyclic * omega-Conotoxins ...
https://pubmed.ncbi.nlm.nih.gov/8386525/?dopt=Abstract
Statistical approach for evolutionary relationship of alpha-conotoxins and members of insulin-superfamilyStatistical approach for evolutionary relationship of alpha-conotoxins and members of insulin-superfamily
... ... Free subject headings]: insulin-superfamily , alpha-conotoxins , evolution , brain secretory peptide , silkmoth bombyx-mori , ...
https://oparu.uni-ulm.de/xmlui/handle/123456789/7850
DeCS - Termos NovosDeCS - Termos Novos
OMEGA-CONOTOXINS OMEGA-CONOTOXINAS ORGANIZADORES EMBRIÔNICOS ORGANIZERS, EMBRYONIC ORGANIZADORES EMBRIONARIOS OXALOBACTER ...
https://decs.bvs.br/P/news2000pie.htm
Professor David J Adams - RMIT UniversityProfessor David J Adams - RMIT University
Nicotinic receptor structure and function probed with conotoxins. Administered by The University of Wollongong.. Funded by: ARC ... beta 2 and beta 4 nicotinic acetylcholine receptor subunits contribute toalpha 3 beta 4 subtype selectivity of alpha-conotoxins ...
https://www.rmit.edu.au/contact/staff-contacts/academic-staff/a/adams-professor-david-j
Neurotoxin - WikipediaNeurotoxin - Wikipedia
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 ... the toxins released by the different types of cone snails include a range of different types of conotoxins, which may be ... "The M-superfamily of Conotoxins: a Review". Cellular and Molecular Life Sciences. 67 (1): 17-27. doi:10.1007/s00018-009-0125-0 ...
https://en.m.wikipedia.org/wiki/Neurotoxin
TCDB » SuperfamiliesTCDB » Superfamilies
Conotoxins (CnTX) are bioactive peptides produced by marine molluscs belonging to Conus genus. The structures of these venomous ...
https://tcdb.org/superfamily.php
Frontiers | Biophysics, pathophysiology, and pharmacology of ion channel gating poresFrontiers | Biophysics, pathophysiology, and pharmacology of ion channel gating pores
2007). muO conotoxins inhibit NaV channels by interfering with their voltage sensors in domain-2. Channels (Austin) 1, 253-262. ...
https://www.frontiersin.org/articles/10.3389/fphar.2014.00053/full
Changing lives through collaborationChanging lives through collaboration
... including a wide variety of neuroactive peptides called conotoxins. Individual conotoxins, generally consisting of 10 to 30 ... About conotoxins The venom of prey hunting cone snails consists of a complex mixture of numerous biologically active components ... The collaboration is targeting new non-opioid drug therapies derived from the group of alpha-conotoxins as analgesic and ... 5Richard T. Layer, and J. Michael McIntosh, Conotoxins: Therapeutic Potential and Application, Mar Drugs. 2006 Apr; 4(3): 119- ...
https://www.grunenthal.com/en/press-room/stories/new-research-partnership-targets-innovative-treatments-for-neuropathic-pain
Sea Snail Venom Could Be the Secret to Less Addictive Painkillers - ExtremeTechSea Snail Venom Could Be the Secret to Less Addictive Painkillers - ExtremeTech
The conotoxins in a geography cone snails venom could hold the key to painkillers that are as effective as (but ... ... Specifically, modified peptides based on the conotoxins from cone snail venom could become the foundation for drugs that safely ... The geography cone snails venom contains chemicals called conotoxins, which are responsible for paralyzing its prey. Though ... scientists from the University of Glasgow have found that the conotoxins contain properties with the potential to change ...
https://www.extremetech.com/extreme/333512-sea-snail-venom-could-be-the-secret-to-less-addictive-painkillers
scn1a Literature [Xenopus] - Xenbase Gene Catalog scn1a Literature [Xenopus] - Xenbase Gene Catalog
μ-Conotoxins that differentially block sodium channels NaV1. .1. through 1.8 identify those responsible for action potentials ...
https://www.xenbase.org/entry/gene/attribution.do?objName=FEATURE&objId=978018&objNameSrt=FEAT&attPage=PAPER&action=VIEW&litOnly=1&att=scn1a&tabId=2&
RCSB PDB - 1FU3: THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIARCSB PDB - 1FU3: THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA
The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. However, the three-dimensional ...
https://www.rcsb.org/structure/1FU3
Wissenschaftliche Publikationen | Max-Planck-GesellschaftWissenschaftliche Publikationen | Max-Planck-Gesellschaft
Dimeric conotoxins VxXIIA, VxXIIB, and VxXIIC from Conus vexillum. Journal of Biological Chemistry 281 (34), S. 24745 - 24755 ( ...
https://www.mpg.de/14597948/publikationen?jahr=2006&seite=2
Cone Snail Venom: The Best Offense Is A Good Defense | Discover MagazineCone Snail Venom: The Best Offense Is A Good Defense | Discover Magazine
An evolutionary tree showing the relatedness between the new worm-hunting snail d-conotoxins and the d-conotoxins found in fish ... Hundreds - and even thousands - of different conotoxins can be found in every Conus species, and each employs its own unique ... These conotoxins werent originally for killing fish - they were used to stun and scare them away. We propose that defensive d ... A slow-moving worm or snail-hunter would have no need of d-conotoxins to stop its prey, and thus its not surprising that ...
https://www.discovermagazine.com/planet-earth/cone-snail-venom-the-best-offense-is-a-good-defense
Honorary Professor David Adams - Queensland Brain Institute - University of QueenslandHonorary Professor David Adams - Queensland Brain Institute - University of Queensland
Transforming conotoxins into cyclotides: backbone cyclization of P-superfamily conotoxins. Peptide Science, 104 (6), 682-692. ... Daly, N. L., Ekberg, J. A., Thomas, L., Adams, D. J., Lewis, R. J. and Craik, D. J. (2004). Structures of mu O-conotoxins from ... Mould, J. A., Alewood, P. F., Lewis, R. J. and Adams, D. J. (2002). Affinity of omega-conotoxins and analogs for N-type calcium ... Callaghan, Brid and Adams, David J. (2010). Analgesic α-conotoxins Vc1.1 and RgIA inhibit N-type calcium channels in sensory ...
https://qbi.uq.edu.au/profile/208/david-adams
2022 - Automated patch clamp screening of amiloride and 5-N,N-hexamethyleneamiloride (HMA) analogs identifies 6-iodoamiloride...2022 - Automated patch clamp screening of amiloride and 5-N,N-hexamethyleneamiloride (HMA) analogs identifies 6-iodoamiloride...
Publications | SchrödingerPublications | Schrödinger
Potency- and Selectivity-Enhancing Mutations of Conotoxins for Nicotinic Acetylcholine Receptors Can Be Predicted Using ...
https://www.schrodinger.com/publications?f%5B0%5D=field_product%3A15002&f%5B1%5D=field_product%3A15017&f%5B2%5D=field_product%3A30604
HELENA SAFAVI - Research - Faculty Profile - The University of UtahHELENA SAFAVI - Research - Faculty Profile - The University of Utah
... and assessment of their role in the oxidative folding of conotoxins. The Journal of biological chemistry. Vol. 285, 12735-46. ...
https://faculty.utah.edu/u0777736-HELENA_SAFAVI/research/index.hml
NeurobiologyNeurobiology
μ-Conotoxins are components of cone snail venom, well-known for their analgesic activity through potent inhibition of voltage- ...
https://www.jbc.org/Neurobiology
Stephen Palumbi's Profile | Stanford Profiles
These conotoxins are associated with trophic diversification and block a diverse array of ion channels and neuronal receptors ... Here we show that conotoxins with little amino acid similarity are in fact products of recently diverged loci that are rapidly ... Gene duplication and diversifying selection result in the formation of functionally variable conotoxins that are linked to ... mRNA transcripts reveal that piscivores from independent evolutionary lineages express the same subset of four-loop conotoxins ...
https://profiles.stanford.edu/stephen-palumbi
Novel Analgesics at a Snails Pace | The Scientist Magazine®Novel Analgesics at a Snail's Pace | The Scientist Magazine®
Despite years of continued research into conotoxins as potential analgesics and a handful of clinical trials testing promising ... magus that have already yielded promising conotoxins, Holford says she can streamline the search for newer peptides that may be ...
https://www.the-scientist.com/features/novel-analgesics-at-a-snails-pace-30150
Browsing Division of Biological Sciences by TitleBrowsing Division of Biological Sciences by Title
Solution Structures and Dynamics of Conotoxins and Small MutS Related Domain from Helicobacter Pylori MutS2  Kumar, Kancherla ...
https://etd.iisc.ac.in/handle/2005/1/browse?rpp=20&sort_by=1&type=title&etal=-1&starts_with=S&order=ASC
PeptidesConusAlpha-conotoxinsAnalgesicNicotinic acetylchInhibitVenomsCalcium ChannelsReceptorsCone snailNAChRsSuperfamilySodium channelsVenomNeuronalSnailsPeptideOmegaDisulfide bondsPharmaceutical applicationsEvolutionarySpeciesStructureToolsFamiliesBeta
Peptides6
  • Conotoxins (conopeptides) are small disulfide bonded peptides from the venom of marine cone snails. (nih.gov)
  • These peptides are named conotoxins . (smartox-biotech.com)
  • Specifically, modified peptides based on the conotoxins from cone snail venom could become the foundation for drugs that safely yet effectively block pain receptors in humans. (extremetech.com)
  • All cone snail venoms consist largely of conotoxins , biologically active peptides that target muscles and neurons. (discovermagazine.com)
  • It's likely they'll find them: there are an estimated 70,000 different conotoxins throughout the sundry species of cone snail, and less than 1% of the peptides have been characterized. (discovermagazine.com)
  • Many small peptides isolated from venoms of cone snails, known as µ-conotoxins, are potent and specific blockers of sodium channels and thus are potential scaffolds for novel analgesics. (edu.au)
Conus5
  • A series of newly discovered ω-conotoxins from Conus catus, including CVID-F, are potent and selective antagonists of N-type VGCCs. (nih.gov)
  • Though this venom can be harmful under normal circumstances (the geography cone snail is the most toxic Conus species), scientists from the University of Glasgow have found that the conotoxins contain properties with the potential to change medicine. (extremetech.com)
  • Identification of a novel class of nicotinic receptor antagonists - Dimeric conotoxins VxXIIA, VxXIIB, and VxXIIC from Conus vexillum. (mpg.de)
  • Hundreds - and even thousands - of different conotoxins can be found in every Conus species, and each employs its own unique combination to paralyze its chosen type of prey. (discovermagazine.com)
  • Identification of Conus peptidylprolyl cis-trans isomerases (PPIases) and assessment of their role in the oxidative folding of conotoxins. (utah.edu)
Alpha-conotoxins1
  • Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. (bvsalud.org)
Analgesic1
  • Authors Adam C. Kennedy, Alessia Belgi, Benjamin W. Husselbee, David Spanswick, Ray S. Norton, Andrea J. Robinson Published Toxins Graphical abstract Abstract Several analgesic α-conotoxins have been isolated from marine cone snails. (andrearobinsongroup.com)
Nicotinic acetylch1
  • α -conotoxins are nicotinic acetylcholine receptor (nAChR) antagonists located in nerves and muscles. (smartox-biotech.com)
Inhibit4
  • Structurally related ω-conotoxins bind directly to and selectively inhibit neuronal (N)-type voltage-gated calcium channels (VGCCs) of nociceptive primary afferent neurones. (nih.gov)
  • Surprisingly, however, α-conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA(B) GPCR mechanism in rat sensory neurones. (nih.gov)
  • δ-conotoxins bind to voltage-dependent sodium channels and inhibit them. (smartox-biotech.com)
  • OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE . (bvsalud.org)
Venoms4
  • Smartox Biotechnology is specialized in chemical synthesis and engineering of conotoxins and other peptide toxins issued from animal venoms. (smartox-biotech.com)
  • A slow-moving worm or snail-hunter would have no need of d-conotoxins to stop its prey, and thus its not surprising that previous studies have not often found d-conotoxins in the predatory venoms of worm or snail-eating species. (discovermagazine.com)
  • The discovery of d-conotoxins in these species, then, would provide evolutionary clues as to the origin of the fish-hunters' venoms. (discovermagazine.com)
  • The present work focuses on understanding the mechanisms of action of two pharmaceutically relevant inhibitor protein systems: the cyclic depsipeptides YM-254890 (YM) and FR900359 (FR) and their target protein, the alpha- (α) subunit of a heterotrimeric G protein as well as conotoxins, venoms obtainable from marine cone snails, which can act as blockers of voltage-gated ion channels. (tu-darmstadt.de)
Calcium Channels2
  • Conotoxins target and block potently a wide range of ion channels, such as voltage-gated sodium channels (Nav), voltage-gated calcium channels (Cav), voltage-gated potassium channels (Kv), nicotinic acetylcholine receptors (nAchRs) as well as other membrane receptors. (smartox-biotech.com)
  • ω -conotoxins are potent inhibitors of N-type voltage-dependent calcium channels (VDCC) [8]. (smartox-biotech.com)
Receptors3
  • Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors (nAChRs). (nih.gov)
  • 2014) Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview. (smartox-biotech.com)
  • Efficient binding of 4/7 α-conotoxins to nicotinic α4β2 receptors is prevented by Arg185 and Pro195 in the α4 subunit. (mpg.de)
Cone snail2
  • The scientists are eager to look for more d-conotoxins in other worm-eating species of cone snail to see if the same defensive strategy is found across many different species. (discovermagazine.com)
  • Despite years of continued research into conotoxins as potential analgesics and a handful of clinical trials testing promising derivatives, however, no cone snail-inspired drugs other than ziconotide have made it to FDA approval. (the-scientist.com)
NAChRs1
  • Some α-conotoxins block nAChRs at the neuromuscular junctions such as α-conotoxin MI, while others are selective blockers of neuronal nAChRs such as α-conotoxin IMI [6]. (smartox-biotech.com)
Superfamily1
  • Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins. (painresearchforum.org)
Sodium channels2
  • μ -conotoxins target voltage-dependent sodium channels (Na v ) preferentially in excitable cells of skeletal muscle. (smartox-biotech.com)
  • 7] Li R., Tomaselli G. (2004) Using the deadly μ-conotoxins as probes of voltage-gated sodium channels. (smartox-biotech.com)
Venom2
  • The geography cone snail's venom contains chemicals called conotoxins, which are responsible for paralyzing its prey. (extremetech.com)
  • 2015. But while the fact that they found these d-conotoxins in snails that should have no need of them is interesting in itself, what was most telling was where they found them: in the part of the venom duct where defensive venom toxins are produced. (discovermagazine.com)
Neuronal1
  • κ-conotoxins target potassium channels and may result in enhanced neuronal excitability. (smartox-biotech.com)
Snails1
  • We propose that defensive d-conotoxins were originally used by ancestral worm-hunting cone snails to protect against threats such as cephalopod and fish predation,' the authors write, 'and have been repurposed for fish-hunting. (discovermagazine.com)
Peptide1
  • Conotoxins are useful molecular tools for studying the properties of their targets in normal and diseases states and can also demonstrate therapeutic interest as peptide-based drugs. (smartox-biotech.com)
Omega3
  • 2013) Omega-conotoxins as experimental tools and therapeutics in pain management. (smartox-biotech.com)
  • Las CONOTOXINAS OMEGA inhiben la entrada de calcio activada por voltaje en la membrana presináptica y, por tanto, la liberación de ACETILCOLINA. (bvsalud.org)
  • loop_ _audit_author.name _audit_author.pdbx_ordinal 'Nielsen, K.J.' 1 'Thomas, L.' 2 'Lewis, R.J.' 3 'Alewood, P.F.' 4 'Craik, D.J.' 5 # _citation.id primary _citation.title ;A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202. (rcsb.org)
Disulfide bonds1
  • α-Conotoxins Vc1.1 and RgIA possess two disulfide bonds and are currently in development as a treatment for neuropathic pain. (nih.gov)
Pharmaceutical applications1
Evolutionary1
  • An evolutionary tree showing the relatedness between the new worm-hunting snail d-conotoxins and the d-conotoxins found in fish-hunting species. (discovermagazine.com)
Species1
  • So scientists from the University of Queensland and Université Montpellier took a combined genetic and proteomic approach to see if they could find d-conotoxins in worm-hunting species - and, lo and behold, they found them. (discovermagazine.com)
Structure1
  • Nicotinic receptor structure and function probed with conotoxins. (edu.au)
Tools1
  • 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)
Families1
Beta1
  • The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. (rcsb.org)
(emedicine.medscape.com)
Changing lives through collaboration
Changing lives through collaboration (grunenthal.com)
RCSB PDB - 1FU3: THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA
RCSB PDB - 1FU3: THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA (rcsb.org)
Wissenschaftliche Publikationen | Max-Planck-Gesellschaft
Wissenschaftliche Publikationen | Max-Planck-Gesellschaft (mpg.de)
Cone Snail Venom: The Best Offense Is A Good Defense | Discover Magazine
Cone Snail Venom: The Best Offense Is A Good Defense | Discover Magazine (discovermagazine.com)
Honorary Professor David Adams - Queensland Brain Institute - University of Queensland
Honorary Professor David Adams - Queensland Brain Institute - University of Queensland (qbi.uq.edu.au)
Publications | Schrödinger
Publications | Schrödinger (schrodinger.com)
HELENA SAFAVI - Research - Faculty Profile - The University of Utah
HELENA SAFAVI - Research - Faculty Profile - The University of Utah (faculty.utah.edu)
Stephen Palumbi's Profile | Stanford Profiles
Stephen Palumbi's Profile | Stanford Profiles (profiles.stanford.edu)
Browsing Division of Biological Sciences by Title
Browsing Division of Biological Sciences by Title (etd.iisc.ac.in)
Short-term synaptic plasticity in layer II/III of the rat anterior cingulate cortex<...
Short-term synaptic plasticity in layer II/III of the rat anterior cingulate cortex<... (abdn.pure.elsevier.com)
Conotoxins: peptide toxins from cone snails
Conotoxins: peptide toxins from cone snails (smartox-biotech.com)
Biosafety Manual - Stanford Environmental Health & Safety
Biosafety Manual - Stanford Environmental Health & Safety (ehs.stanford.edu)
The Top 10 Deadliest Animals in the World - AZ Animals
The Top 10 Deadliest Animals in the World - AZ Animals (a-z-animals.com)
Stanley A Thayer - Research output - Experts@Minnesota
Stanley A Thayer - Research output - [email protected] (experts.umn.edu)
Are ticks venomous animals? | Frontiers in Zoology | Full Text
Are ticks venomous animals? | Frontiers in Zoology | Full Text (frontiersinzoology.biomedcentral.com)
28.4 Superphylum Lophotrochozoa: Molluscs and Annelids - Biology 2e | OpenStax
28.4 Superphylum Lophotrochozoa: Molluscs and Annelids - Biology 2e | OpenStax (openstax.org)
Xuejun Zhang, Ph.D. | Harvard Catalyst Profiles | Harvard Catalyst
Xuejun Zhang, Ph.D. | Harvard Catalyst Profiles | Harvard Catalyst (connects.catalyst.harvard.edu)
Lourdes Cruz Biography, Contribution To Science - PeoPlaid Profile
Lourdes Cruz Biography, Contribution To Science - PeoPlaid Profile (peoplaid.com)
杀虫活性多肽研究进展
杀虫活性多肽研究进展 (nyxxb.cn)
Warnings: Corona+GENE vaccine = snake venom 02 - news 01 - since 2020
Warnings: Corona+GENE vaccine = snake venom 02 - news 01 - since 2020 (med-etc.com)
ConoServer
ConoServer (conoserver.org)
(emedicine.medscape.com)
BRAIN 2025 Report | Brain Initiative
BRAIN 2025 Report | Brain Initiative (nih.gov)
Underwater pharmacy: Meet the scientists raiding the ocean's medicine cabinet | BBC Science Focus Magazine
Underwater pharmacy: Meet the scientists raiding the ocean's medicine cabinet | BBC Science Focus Magazine (sciencefocus.com)
Sea Snail Venom Could Lead to New Painkillers
Sea Snail Venom Could Lead to New Painkillers (medscape.com)
MeSH Browser
MeSH Browser (meshb.nlm.nih.gov)
Publications - Molecular Genomics Core | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Publications - Molecular Genomics Core | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development (nichd.nih.gov)