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At least 19 recordsLinked to original sources
PubMed2005

Intraspecific variation of venom injected by fish-hunting Conus snails.

Venom peptides from two species of fish-hunting cone snails (Conus striatus and Conus catus) were characterized using microbore liquid chromatography coupled with matrix-assisted laser desorption/ionization-time of flight-mass spectrometry and electrospray ionization-ion trap-mass spectrometry. Both crude venom isolated from the venom duct and injected venom obtained by milking were studied. Based on analysis of injected venom samples from individual snails, significant intraspecific variation (i.e. between individuals) in the peptide complement is observed. The mixture of peptides in injected venom is simpler than that in the crude duct venom from the same snail, and the composition of crude venom is more consistent from snail to snail. While there is animal-to-animal variation in the peptides present in the injected venom, the composition of any individual's injected venom remains relatively constant over time in captivity. Most of the Conus striatus individuals tested injected predominantly a combination of two neuroexcitatory peptides (s4a and s4b), while a few individuals had unique injected-venom profiles consisting of a combination of peptides, including several previously characterized from the venom duct of this species. Seven novel peptides were also putatively identified based on matches of their empirically derived masses to those predicted by published cDNA sequences. Profiling injected venom of Conus catus individuals using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry demonstrates that intraspecific variation in the mixture of peptides extends to other species of piscivorous cone snails. The results of this study imply that novel regulatory mechanisms exist to select specific venom peptides for injection into prey.

Animals↗
PubMed1998

Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail.

Conantokin-G isolated from the marine snail Conus geographus is a 17-amino acid gamma-carboxyglutamate (Gla)-containing peptide that inhibits the N-methyl-D-aspartate receptor. We describe the cloning and sequence of conantokin-G cDNA and the possible role of the propeptide sequence. The cDNA encodes a 100amino acid peptide. The N-terminal 80 amino acids constitute the prepro-sequence, and the mature peptide is derived from the remaining C-terminal residues after proteolysis, C-terminal amidation, and a unique post-translational modification, gamma-carboxylation of glutamate residues to Gla. Mature conantokin-G peptide containing Glu residues (E.Con-G) in place of Gla is a poor substrate for the vitamin K-dependent gamma-glutamyl carboxylase (apparent Km = 3.4 mM). Using peptides corresponding to different segments of the propeptide we investigated a potential role for the propeptide sequences in gamma-carboxylation. Propeptide segment -20 to -1 covalently linked to E.Con-G or the synthetic pentapeptide FLEEL increased their apparent affinities 2 orders of magnitude. These substrates are not efficiently carboxylated by the bovine microsomal gamma-glutamyl carboxylase, suggesting differences in specificities between the Conus and the mammalian enzyme. However, the role of propeptide in enhancing the efficiency of carboxylation is maintained.

1-Carboxyglutamic Acid↗
PubMed2003

CGX-1051, a peptide from Conus snail venom, attenuates infarction in rabbit hearts when administered at reperfusion.

CGX-1051, isolated from the venom of the marine snail Conus purpurasens, was previously noted to interact with potassium channels. Since potassium channels play an important role in cardiac physiology, we assessed the effect of CGX-1051 on infarct size in a rabbit heart model of ischemia/reperfusion. A coronary branch was occluded for 30 minutes followed by 3 hours of reperfusion in in situ and 2 hours in in vitro preparations. Infarct size was measured with triphenyltetrazolium chloride staining and expressed as a percent of the risk zone. In in situ studies, a bolus intravenous injection of CGX-1051, either 10 or 100 microg/kg, administered 5 minutes before reperfusion, reduced infarct size from 40.4 +/- 2.8% of the risk zone in untreated animals to 19.8 +/- 3.8% and 15.0 +/- 1.9%, respectively. One microg/kg CGX-1051 was not protective. To see if the salvage was sustained, two groups of rabbits underwent 72 hours of reperfusion. The dose of 10 microg/kg infused 5 minutes before reperfusion reduced infarct size from 37.0 +/- 1.6% in untreated rabbits to 15.5 +/- 2.0%. When administered 10 minutes after reperfusion had begun, 100 microg/kg CGX-1051 had no effect. CGX-1051 also reduced infarct size in crystalloid-perfused, isolated rabbit hearts suggesting that protection did not depend on circulating leukocytes. The mitochondrial KATP inhibitors glibenclamide and 5-hydroxydecanoate and the MEK(1/2), ERK and hence, inhibitor PD 98059 aborted protection from CGX-1051. These data indicate that functionally active ERK and mitochondrial KATP channels are necessary for protection. CGX-1051 caused no hemodynamic alterations at any dose tested. We conclude that CGX-1051 has a powerful anti-infarct effect when given just before reperfusion.

Animals↗
PubMed1993

Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus snail.

TxIA and TxIB, peptides with 27-amino acid residues recently isolated from the molluscivorous marine snail Conus textile neovicarius, exhibit strong paralytic activity in molluscs, with no paralytic effects on athropods and vertebrates. At concentrations of 0.25-0.5 microM the toxins cause spontaneous repetitive firing and dramatic broadening of the action potential of cultured Aplysia neurons. The action potential duration partially recovers within 30 min in the presence of the toxins. Under these conditions a second toxin application does not change the spike duration. TxI-induced spike broadening occurs when potassium and calcium conductances are blocked. Voltage-clamp experiments revealed that the toxins alter the kinetics of the sodium current either by slowing down the rate of sodium current inactivation or by recruiting silent sodium channels with slower activation and inactivation kinetics. The toxins shift the voltage-dependent steady-state Na+ current inactivation curve to more positive values by 6 mV. These changes are not associated with alteration in the rate of sodium current activation, in the peak sodium current, or the sodium current reversal potential. TxI apparently represents a new class of conotoxins with an unusual phylogenic specificity and may therefore be useful as a probe for the study of molluscan neuronal sodium channels.

Animals↗
PubMed2005

Clinico-toxinological characterization of the acute effects of the venom of the marine snail, Conus loroisii.

The venom of the marine snail, Conus loroisii, was studied to assess its risk and lethal factors in regard of human welfare. The lethality of the crude venom (LD50-5.0 mg/kg via i.p.) in mice was associated with reduced motor activity, asphyxiation, followed by respiratory failure. The effects on vital tissues revealed vascular congestion and inflammatory cell infiltration around the portal triad of the liver, spongiosis of the brain, hemorrhages/congested blood vessels in lung and endothelial cells of the renal tubule. Repeated measures of hematological profiles indicated that the venom significantly reduced erythrocytes (P<0.001, GLM repeated measures), followed associated with depletion of hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and platelet count. Serum enzymes such as, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase and alkaline and acid phosphatases were altered significantly (P<0.05, Friedman test), which in turn confirmed the damage of vital organ tissues. Dual effect of the venom on the activity of mouse brain acetylcholinesterase stand for concentration specific, whereas maximal inhibition (60.41%, P<0.05, Wilcoxon signed rank test) in erythrocyte acetylcholinesterase did not show the dual activity observed in brain. The Ciphergen ProteinChip analysis of the envenomed serum further revealed that the venom causes changes in definite molecules involved in inflammatory process and ionic transport. In all, the venom of C. loroisii is potentially lethal to mammals, through its rapid action on the central and peripheral nervous systems by blocking neurotransmission with selective interference of ionic channels/receptors.

Animals↗
PubMed1997

Identification of a vitamin K-dependent carboxylase in the venom duct of a Conus snail.

Peptides from the venom ducts of cone snails (genus Conus) contain gamma-carboxyglutamate residues. The gamma-glutamyl carboxylase responsible for this post-translational modification is localized in the microsomal fraction, strictly dependent on vitamin K, activated by ammonium sulfate, and is associated with endogenous substrate. The K(m) of the enzyme for vitamin K is comparable to that for the bovine carboxylase. However, a propeptide containing substrate related to the blood coagulation protein factor IX, a highly efficient substrate for the bovine enzyme, was poorly carboxylated by the Conus enzyme, suggesting differences in gamma-carboxylase recognition signal sequences and/or structural requirements at the carboxylation site.

1-Carboxyglutamic Acid↗
PubMed1983

Tessulatoxin, the vasoactive protein from the venom of the marine snail Conus tessulatus.

1. Tessulatoxin, a powerful vasoactive protein from the marine snail Conus tessulatus, has been purified by affinity and electrofocusing chromatography. 2. The purified protein is almost homogeneous on slab gel electrophoresis. 3. The molecular weight of tessulatoxin is 26,000: the lethal dose for the fish Rhodeus ocellatus smithi is 1 microgram/g. 4. This toxic protein (10(-7) approximately 5 X 10(-7) g/ml) causes a marked contraction of the rabbit isolated aorta, which is inhibited by verapamil (10(-6) M).

Animals↗
PubMed1992

Inhibition of evoked neurotransmitter release from rat hippocampus by a polypeptide toxin isolated from the marine snail Conus distans.

The active fraction, isolated and partially purified from the crude venom of the marine snail Conus distans, with a molecular mass of about 25 kDa, inhibits neurotransmitter release in rat hippocampus. This toxin (distans Toxin) inhibits the electrically evoked tritium labelled noradrenaline release from rat hippocampal slices in a dose and time dependent manner. The neurotransmitter release is mainly regulated by N-type of voltage sensitive Ca(2+)-channels. The distans toxin behaves as a partial antagonist of calcium in the buffer, possibly by competing with calcium for this type of voltage sensitive Ca(2+)-channels.

Animals↗
PubMed1986

Purification, subunit structure and pharmacological effects on cardiac and smooth muscle cells of a polypeptide toxin isolated from the marine snail Conus tessulatus.

The most active component in smooth muscle contraction, isolated from the whole venom of the marine snail Conus tessulatus, has a molecular mass of about 55 kDa. The toxin protein, tessulatus toxin, appeared to be constituted by two distinct polypeptide bands of 26 kDa and 29 kDa. The pure toxin caused a marked contraction of both guinea-pig ileum and rabbit aorta at nanomolar concentrations. Tessulatus-toxin-induced contraction was indirectly prevented by classical inhibitors of the voltage-dependent Ca2+ channel. Tessulatus toxin caused a large increase in the initial rate of 45Ca2+ uptake by cardiac cells. This uptake was insensitive to Ca2+ channel blockers at concentrations 100-1000 fold higher than those known to block voltage-dependent Ca2+ channels in these cells. Voltage clamp experiments have confirmed that tessulatus toxin was not directly active on the Ca2+ current. Tessulatus-toxin-stimulated 45Ca2+ influx was inhibited by dichlorobenzamil and suppressed when Na+ was substituted by Li+, indicating that the toxin acted via activation of the Na+/Ca2+ exchange system in cardiac cells. Activation by tessulatus toxin of the Na+/Ca2+ exchange system occurred via a toxin-stimulated Na+ entry into cardiac cells and was observed in the same range of toxin concentration which produced 45Ca2+ entry. The Na+ entry system that was activated by tessulatus toxin was insensitive to classic inhibitors of known Na+ entry systems in cardiac cells. Possible mechanisms by which tessulatus toxin induced Na+ entry into cardiac cells and contractions in smooth muscles are discussed. Tessulatus toxin is cytotoxic when used at high concentrations.

Animals↗
PubMed2005

Amino acid sequence and biological activity of a gamma-conotoxin-like peptide from the worm-hunting snail Conus austini.

A novel 31-residue toxin, named as7a, was isolated and characterized from the venom of Conus austini, a vermivorous cone snail collected in the western Gulf of Mexico. The complete amino acid sequence, TCKQKGEGCSLDVgammaCCSSSCKPGGPLFDFDC, was determined by automatic Edman sequencing after reduction and alkylation. The sequence shows six Cys residues arranged in the pattern that defines the O-superfamily of conotoxins, and the sequence motif -gammaCCS-, which has only been found in the gamma-conotoxin family. The molecular mass of the native peptide was determined by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, which confirmed the chemical analyses and suggested a free C-terminus. The purified peptide elicited toxic effects in the freshwater snail Pomacea paludosa after intramuscular injection, but it had no effect when injected intracerebrally into mice. The structural similarity of peptide as7a to other gamma-conotoxins suggests that modulation of pacemaker channels could be responsible for its biological activity.

Amino Acid Sequence↗
PubMed1995

Conodipine-M, a novel phospholipase A2 isolated from the venom of the marine snail Conus magus.

We describe the purification and first biochemical characterization of an enzymatic activity in venom from the marine snail Conus magus. This enzyme, named conodipine-M, is a novel phospholipase A2 with a molecular mass of 13.6 kDa and is comprised of two polypeptide chains linked by one or more disulfide bonds. The amino acid sequence of conodipine-M shows little if any homology to other previously sequenced phospholipase A2 enzymes (PLA2s). Conodipine-M thus represents a new group of PLA2s. This is remarkable, since conodipine-M displays a number of properties that are similar to those of previously characterized 14-kDa PLA2s. The enzyme shows little, if any, phospholipase A1, diacyglycerol lipase, triacylglycerol lipase, or lysophospholipase activities. Conodipine-M hydrolyzes the sn-2 ester of various preparations of phospholipid only in the presence of calcium and with specific activities that are comparable to those of well known 14-kDa snake venom and pancreatic PLA2s. The Conus enzyme binds tightly to vesicles of the negatively charged phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphomethanol and catalyzes the hydrolysis of this substrate in a processive fashion. Conodipine-M does not significantly discriminate against phospholipids with unsaturated versus saturated fatty acids at the sn-2 position or with different polar head groups. Linoleoyl amide and a phospholipid analog containing an alkylphosphono group at the sn-2 position are potent inhibitors of conodipine-M. We suggest that the functional resemblance of conodipine-M to other PLA2s might be explained by the utilization of similar catalytic residues.

Amino Acid Sequence↗
PubMed1996

Mass spectrometric-based revision of the structure of a cysteine-rich peptide toxin with gamma-carboxyglutamic acid, TxVIIA, from the sea snail, Conus textile.

A mollusk-specific toxin, TxVIIA, having potent paralytic activity was isolated from the venom of sea snail Conus textile (Fainzilber M et al., 1991, Eur J Biochem 202:589-595). The structure reported above was based upon amino acid analysis and the Edman degradation. We have recently reinvestigated this toxin employing some of the most novel techniques in mass spectrometry. We now report a revised structure based primarily on high-energy collision-induced dissociation analysis of the two Asp17-N peptides of the reduced, pyridinylethyl derivative representing the entire sequence using matrix-assisted laser desorption ionization (MALDI) as CGGYSTYC gamma VDS gamma CCSDNCVRSYCTLF-NH2 (gamma, gamma-carboxyglutamic acid or Gla). The N-terminus of the previous sequence was incorrect, apparently due to a side reaction of reduction and alkylation, which led to the erroneous assignment of Trp for the N-terminal residue. In addition, the last two C-terminal amino acids and the C-terminal amidation had not been detected. Also, a combination of electrospray ionization mass spectrometry and positive and negative ion MALDI mass spectrometry provided information on the molecular weights of the native and derivatized toxin and presence of two Gla residues. Thus, TxVIIA does not have an "unusual" sequence as previously reported, but in fact belongs to the conserved Cys framework for omega- and delta-conotoxins. However, the four net negative charges with the cysteine-rich structure of this revised sequence is highly unusual for conopeptides.

1-Carboxyglutamic Acid↗
PubMed2004

A novel 13 residue acyclic peptide from the marine snail, Conus monile, targets potassium channels.

A novel 13-residue peptide Mo1659 has been isolated from the venom of a vermivorous cone snail, Conus monile. HPLC fractions of the venom extract yielded an intense UV absorbing fraction with a mass of 1659Da. De novo sequencing using both matrix assisted laser desorption and ionization and electrospray MS/MS methods together with analysis of proteolytic fragments successfully yielded the amino acid sequence, FHGGSWYRFPWGY-NH(2). This was further confirmed by comparison with the chemically synthesized peptide and by conventional Edman sequencing. Mo1659 has an unusual sequence with a preponderance of aromatic residues and the absence of apolar, aliphatic residues like Ala, Val, Leu, and Ile. Mo1659 has no disulfide bridges distinguishing it from the conotoxins and bears no sequence similarity with any of the acyclic peptides isolated thus far from the venom of cone snails. Electrophysiological studies on the effect of Mo1659 on measured currents in dorsal root ganglion neurons suggest that the peptide targets non-inactivating voltage-dependent potassium channels.

Amino Acid Sequence↗
PubMed1987

Actions of a polypeptide toxin from the marine snail Conus striatus on voltage-sensitive sodium channels.

The effects of a polypeptide toxin of 25,000 Da from the marine snail Conus striatus (CsTx) on sodium channels in mouse neuroblastoma cells and rat brain synaptosomes were studied. CsTx slowed sodium channel inactivation without altering the time course of activation of the channels. The voltage dependence of sodium channel inactivation was shifted to more negative membrane potentials and made less steep. Peak sodium currents were increased, and the voltage dependence of activation was shifted to more negative membrane potentials. The action of the toxin was voltage-dependent. Maximum toxin effects were observed at membrane potentials in the range of -100 to -60 mV. Apparent KD values were calculated assuming a one-to-one binding interaction. At more positive membrane potentials, the apparent KD for toxin action increased e-fold for each 19-mV depolarization. Apparent KD also increased at membrane potentials more negative than -100 mV. CsTx did not have significant effects on the binding of saxitoxin or Leiurus alpha-scorpion toxin to their receptor sites on sodium channels. CsTx enhanced the binding of batrachotoxinin A 20-alpha-benzoate to sodium channels in the same concentration range as its physiological effects. It is concluded that CsTx interacts with a new receptor site on the extracellular surface of the sodium channel at which specific effects on channel inactivation can occur.

Animals↗
PubMed1997

Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus.

Conantokin G is a gamma-carboxyglutamic acid- (Gla-) containing conotoxin isolated from the venom of the marine cone snail Conus geographus. This 17-residue polypeptide, which contains five gamma-carboxyglutamic acid residues, is a N-methyl-d-aspartate- (NMDA-) type glutamate receptor antagonist. To investigate the role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, we determined the three-dimensional structure of the conantokin G/Ca2+ complex by two-dimensional 1H NMR spectroscopy and compared it to the high-resolution structure of conantokin G in the absence of metal ions [Rigby et al. (1997) Biochemistry 36, 6906]. Complete resonance assignments were made by two dimensional 1H NMR spectroscopy at pH 5.6 in the presence of saturating amounts of Ca2+. Distance geometry and simulated annealing methods were used to derive 23 convergent structures from a set of 302 interproton distance restraints and two torsion angle measurements. A high-resolution structure, with the backbone root mean square deviation to the geometric average of the 23 structures of 0.6 +/- 0.1 A, contains a linear alpha-helix from Gla 3 to Lys 15. Gla residues 3, 7, 10, and 14 are aligned in a linear array on one face of the helix. A genetic algorithm was applied to determine the calcium positions in conantokin G, and the conantokin G/Ca2+ complex refined by molecular simulation. Upon binding of Ca2+ to gamma-carboxyglutamic acid, conantokin G undergoes a conformational transition from a distorted curvilinear 310 helix to a linear alpha-helix. Occupancy of the metal binding sites, defined by gamma-carboxyglutamic acids, results in formation of a calcium-carboxylate network that linearizes the helix and exposes the hydrophobic amino acids on the opposite face of the helix.

1-Carboxyglutamic Acid↗
PubMed2001

Contryphan-Vn: a novel peptide from the venom of the Mediterranean snail Conus ventricosus.

The isolation, purification, and biochemical characterization of the novel peptide Contryphan-Vn, extracted from the venom of the Mediterranean marine snail Conus ventricosus, is reported. Contryphan-Vn is the first Conus peptide described from a vermivorous species and the first purified from the venom of the single Mediterranean Conus species. The amino acid sequence of Contryphan-Vn is As with other contryphans, Contryphan-Vn contains a d-tryptophan residue, is amidated at the C-terminus, and maintains the five-residue intercystine loop size. However, Contryphan-Vn differs from the known contryphans by the insertion of the Asp residue at position 2, by the lack of hydroxylation of Pro(4), and, remarkably, by the presence of the basic residue Lys(6) within the intercystine loop. Although the biological function(s) of contryphans is still unknown, these characteristics suggest distinct molecular target(s) and/or function(s) for Contryphan-Vn.

Alkylation↗
PubMedDate not supplied

Two polypeptide toxins with opposite effects on calcium uptake in bovine chromaffin cells: isolation from the venom of the marine snail Conus distans.

Two polypeptide toxins which modulate the uptake of 45Ca2+ in bovine chromaffin cells were isolated from the venom of the marine snail Conus distans. The molecular weights were estimated by gel electrophoresis and gel filtration to be 25.5 and 24 kDa, respectively. The purified proteins were electrophoretically homogeneous. The 25.5 kDa-component caused a concentration-dependent increase of the initial rate of 45Ca2+ uptake, but it had no effect on the stimulation evoked uptake. The 24 kDa-component produced the opposite effects; it caused a concentration-dependent inhibition of the stimulation evoked 45Ca2+ uptake, but it did not affect the initial rate.

Animals↗