Carboxyglutamate in a Neuroactive Toxin (original) (raw)
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A sleep-inducing peptide from Conus geographus venom
Toxicon : official journal of the International Society on Toxinology, 1985
A novel peptide toxin, which causes a sleep-like state upon intracerebral injection in mice, has been purified to homogeneity from the venom of the piscivorous marine snail Conus geographus L. It elicits no obvious effects when injected i.p. into either mice or fish. The purified toxin is a highly acidic heptadecapeptide with no cystine residues (Lys1, Arg1, Asx2, Ser1, Glx7-8, Gly1, Ile1, Leu2). This composition is in marked contrast to those of other conotoxins, which are basic and disulphide-bridged. The N-terminal residue is Gly and the COOH-terminal sequence is Ser-Asn-NH2.
Gamma-carboxyglutamate in a neuroactive toxin
Journal of Biological Chemistry, 1984
The venom of a fish-hunting cone snail (Conus geographus) contains a novel toxin, the "sleeper" peptide, which induces a sleep-like state in mice when injected intracerebrally. We demonstrate that this peptide contains 5 mol of y-carboxyglutamate (Gla) in 17 amino acids. The amino acid sequence of the sleeper peptide is
Peptide toxins from Conus geographus venom
Journal of Biological Chemistry, 1981
Three homologous toxic peptides which cause postsynaptic inhibition at the vertebrate neuromuscar junction have been purified from the venom of the marine snail Conus geographus.
Isolation and structure of a peptide toxin from the marine snail Conus magus
Archives of Biochemistry and Biophysics, 1982
A ll-residue peptide toxin has been isolated from the venom of the marine snail Conus magus. Its amino acid sequence, Gly-Arg-Cys-Cys-His-Pro-Ala-Cys-Gly-Lys-Asn-Tyr-Ser-Cys-NHz, is homologous with those of the previously described conotoxins GI, GII, and GIA from Conus geographus. The new peptide, conotoxin MI, is two to three times more active than the others, and is presumed to act as they do at the acetylcholine receptor of vertebrate neuromuscular junctions. 329
Toxicon, 1981
from the venom of the marine snail Conus geographus which acts on the vertebrate central nervous system. Toxicon 19, 691-699, 1981 .-A toxin from the venom of the marine snail, Conus geographus Linne, has been purified to homogeneity and characterized. The toxin is a heat stable acidic protein with an apparent monomer mol. wt of 13,000. It has no detectable toxicity to mice on i.p. injection, but is a potent convulsant following intracerebral injection. Thus, it is distinct from other toxins in the venom which act on the peripheral neuromuscular system .
Novel γ-carboxyglutamic acid-containing peptides from the venom of Conus textile
FEBS Journal, 2006
Venom from marine snails of the genus Conus contains a plethora of highly potent neurotoxins, many of which block voltage-and ligand-gated ion channels. The peptides are typically 12-30 amino acids in length and contain disulfide bonds and a wide variety of post-translationally modified amino acids [1,2]. Particularly abundant are 4-trans-hydroxyproline (Hyp), 6-lbromotryptophan (BrTrp) and c-carboxyglutamic acid (Gla) .
ACS Omega, 2019
Many conotoxins, natural peptides of marine cone snails, have been identified to target neurons. Here, we provide data on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali. The identified definitive pharmacological families possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho). These classes shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage-gated K channels, and α1-adrenoceptors, respectively. The VI/VII-O3 conotoxins might be prospected as an inhibitor of N-methyl-Daspartate. Con-ikot-ikot could be applied as an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blocker medicine. The definitive pharmacology classes of conotoxins as well as those yet to be elucidated need to be further established and verified.
Toxicon, 2014
The toxinology of the crassispirine snails, a major group of venomous marine gastropods within the superfamily Conoidea, is largely unknown. Here we define the first venom peptide superfamily, the P-like crassipeptides, and show that the organization of their gene sequences is similar to conotoxin precursors. We provide evidence that one peptide family within the P-like crassipeptide superfamily includes potassium-channel (K-channel) blockers, the κP-crassipeptides. Three of these peptides were chemically synthesized (cce9a, cce9b and iqi9a). Using conventional electrophysiology, cce9b was shown to be an antagonist of both a human K V 1.1 channel isoform (Shaker subfamily of voltage-gated K channels) and a Drosophila K-channel isoform. We assessed the bioactivity of these peptides in native mammalian dorsal root ganglion neurons in culture. We demonstrate that two of these crassipeptides, cce9a and cce9b, elicited an excitatory phenotype in a subset of small-diameter capsaicin-sensitive mouse DRG neurons that were also affected by κJ-conotoxin pl14a, a blocker of K V 1.6 channels. Given the vast potential complexity of heteromeric K-channel isoforms, this study demonstrates that the crassispirine venoms are a potentially rich source for discovering novel peptides that can help to identify and characterize the diversity of K-channel subtypes expressed in native neurons and other cell types.
Peptides, 2013
Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named ␣-conotoxin TxIC. We assign this conopeptide to the 4/7 ␣-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, ␣-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 M, <5% inhibition), compared to its high paralytic potency in invertebrates, PD 50 = 34.2 nMol kg −1 . The non-post-translationally modified form, [Pro] 2,8 [Glu] 16 ␣-conotoxin TxIC, demonstrates differential selectivity for the ␣32 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC 50 of 5.4 ± 0.5 M. Interestingly its comparative PD 50 (3.6 Mol kg −1 ) in invertebrates was ∼100 fold more than that of the native peptide. Differentiating ␣-conotoxin TxIC from other ␣-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of ␥-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of ␣-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.