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H Schweitz

Publications and source records attributed to H Schweitz.

At least 37 records · Page 2Linked to original sources
PubMed1988

The secondary structure of the toxin ATX Ia from Anemonia sulcata in aqueous solution determined on the basis of complete sequence-specific 1H-NMR assignments.

The toxin preparations ATX I, ATX Ia and ATX Ib from Anemonia sulcata were investigated by proton nuclear magnetic resonance (NMR). High-resolution phase-sensitive two-dimensional NMR experiments were used to monitor the separation by high-performance liquid chromatography of the two isoproteins ATX Ia and ATX Ib. For ATX Ia complete sequence-specific resonance assignments were obtained and the secondary structure was determined. To obtain the NMR assignments we used a variant of the sequential assignment technique which relied extensively on cross-peak fine-structure analysis in phase-sensitive spectra, using spectrum simulations based on density matrix calculations with the program SPHINX. These procedures, which resulted in extensive amino acid spin system identifications prior to the sequential assignments, should be generally applicable for small proteins with relatively narrow 1H-NMR lines. The secondary structure of ATX I includes a beta sheet consisting of four strands. No evidence was found for the presence of regular helical segments. The four beta strands are connected by two extended loops and a tight turn, for which further characterization has to await the complete determination of the three-dimensional structure.

Amino Acid Sequence↗
PubMed1987

The amino acid sequence of toxin RpIII from the sea anemone, Radianthus paumotensis.

The amino acid sequence of the sodium channel toxin RpIII from the sea anemone Radianthus paumotensis has been determined. The protein is homologous with five analogous toxins from three anemone species, and is most similar to a less toxic protein, RpII, from the same organism. Twelve residues are conserved in all six toxins, one of which is an arginine residue thought to be essential for toxicity. The others (Cys, Gly, Pro and Trp) tend to be conserved in other sets of homologous proteins to maintain functional folds. Comparisons of the sequences suggest the existence of two separate but related classes of toxins cumon the three species of anemone.

Amino Acid Sequence↗
PubMed1987

Crystal structure of a snake venom cardiotoxin.

Cardiotoxin VII4 from Naja mossambica mossambica crystallizes in space group P61 (a = b = 73.9 A; c = 59.0 A) with two molecules of toxin (molecular mass = 6715 Da) in the asymmetric unit. The structure was solved by using a combination of multiple isomorphous replacement and density modification methods. Model building and least-squares refinement led to an agreement factor of 27% for a data set to 3-A resolution prior to any inclusion of solvent molecules. The topology of the molecule is similar to that found in short and long snake neurotoxins, which block the nicotinic acetylcholine receptor. Major differences occur in the conformation of the central loop, resulting in a change in the concavity of the molecule. Hydrophobic residues are clustered in two distinct areas. The existence of stable dimeric entities in the crystalline state, with the formation of a six-stranded antiparallel beta sheet, may be functionally relevant.

Amino Acid Sequence↗
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↗
PubMed1986

A polypeptide toxin from the coral Goniopora. Purification and action on Ca2+ channels.

A polypeptide toxin has been isolated from Goniopora coral with an Mr of 19 000. Goniopora toxin has the following properties: it induces contraction of guinea pig ileum and this contraction is prevented by Ca2+-channel blockers; it stimulates 45Ca2+ influx in cardiac cells in culture and this stimulation is abolished by Ca2+-channel blockers; it prevents binding of (+)-[3H]PN 200-110 to the Ca2+-channel protein of skeletal muscle T-tubule membranes. All these results taken together suggest that Goniopora toxin is a Ca2+-channel activator.

Animals↗
PubMed1986

The interaction of polypeptide neurotoxins with tetrodotoxin-resistant Na+ channels in mammalian cardiac cells. Correlation with inotropic and arrhythmic effects.

This paper describes the interaction of several polypeptide neurotoxins isolated from sea anemone toxins and scorpion venom with the tetrodotoxin-resistant Na+ channel of rat cardiac cells. The 22Na+ flux and tension development were measured to examine in parallel the cardiotonic and cardiotoxic effects of these polypeptides. Inotropic effects and arrhythmias were seen in the concentration range in which an action of the toxins on the Na+ channel was observed. The maximal inotropic effect was systematically observed at toxin concentrations below the concentration value observed for half-maximal stimulation of 22Na+ flux through the Na+ channel. Arrhythmias began at concentrations near the value for half-maximal stimulation of 22Na+ flux by the toxins. Toxins extracted from the sea anemones Anemonia sulcata and Anthopleura xanthogrammica were more active than scorpion toxins and sea anemone Radianthus paumotensis toxins. The most interesting among all the toxins tested for potential use in cardiotherapy was toxin II from Anthopleura xanthogrammica.

Animals↗
PubMed1985

Purification, sequence, and pharmacological properties of sea anemone toxins from Radianthus paumotensis. A new class of sea anemone toxins acting on the sodium channel.

Four new toxins have been isolated from the sea anemone Radianthus paumotensis: RpI, RpII, RpIII, and RpIV. They are polypeptides comprised of 48 or 49 amino acids; the sequence of RpII has been determined. Toxicities of these toxins in mice and crabs are similar to those of the other known sea anemone toxins, but they fall into a different immunochemically defined class. The sequence of RpII shows close similarities with the N-terminal end (up to residue 20) of the previously sequenced long sea anemone toxins, but most of the remaining part of the molecule is completely different. Like the other sea anemone toxins, Radianthus toxins are active on sodium channels; they slow down the inactivation process. Through their Na+ channel action, Radianthus toxins stimulate Na+ influx into tetrodotoxin-sensitive neuroblastoma cells and tetrodotoxin-resistant rat skeletal myoblasts. The efficiency of the toxins is similar in the two cellular systems. In that respect, Radianthus toxins behave much more like scorpion neurotoxins than sea anemone toxins from Anemonia sulcata or Anthopleura xanthogrammica. In binding experiments to synaptosomal Na+ channels, Radianthus toxins compete with toxin II from the scorpion Androctonus australis but not with toxins II and V from Anemonia sulcata.

Amino Acid Sequence↗
PubMed1984

Crystallization and preliminary x-ray investigation of a protein neurotoxin from the sea anemone Anthopleura xanthogrammica.

Neurotoxic protein AX-I isolated from the sea anemone Anthopleura xanthogrammica has been crystallized. Two crystal forms were obtained. One form is tetragonal, space group P41 or P43 , with cell dimensions a = b = 40.74(2) A and c = 34.13(3) A. The second crystal form is hexagonal, space group P622 , with cell dimensions a = b = 72.23(2) A and c = 39.16(2)A. Density measurements indicate that the tetragonal crystals contain one toxin molecule/asymmetric unit. Both crystal forms diffract to high resolution.

Animals↗
PubMed1984

Lethal potency in mice of toxins from scorpion, sea anemone, snake and bee venoms following intraperitoneal and intracisternal injection.

The lethal potency of 29 toxins from scorpion, sea anemone, snake and bee venoms was studied. Lethality following intracisternal injection of these toxins is considerably higher than following i.p. injection (except for the snake neurotoxins). This is of practical interest in the determination of the concentration of active toxins in a solution when only small amounts are available, as in the case of radiolabelled toxins.

Animals↗
PubMed1984

A micro-radioimmunoassay for apamin.

A radioimmunoassay is described which allows detection of quantities of apamin between 5 and 1200 fmoles (10-2400 pg) in 50 microliter aliquots. The assay requires a few milliliters of apamin antiserum diluted 10,000-20,000 times and 125I apamin at a specific radioactivity of 2000 Ci/mmole. This assay is specific for apamin.

Apamin↗
PubMed1984

The interaction of sea anemone and scorpion neurotoxins with tetrodotoxin-resistant Na+ channels in rat myoblasts. A comparison with Na+ channels in other excitable and non-excitable cells.

The properties of interactions of several polypeptide neurotoxins isolated from sea anemone and scorpion venom with Na+ channels of rat myoblasts, chick myotubes, neuroblastoma cells, and fibroblasts have been compared. Tetrodotoxin (TTX)-resistant Na+ channels appear to be much more sensitive to the action of sea anemone toxins than TTX-sensitive Na+ channels but have the same affinity for scorpion neurotoxins. This conclusion holds both for Na+ channels that can be activated electrically and for silent forms of Na+ channels. The sensitivity to sea anemone toxins of the different types of Na+ channels that have been studied suggests the existence of multiple forms of Na+ channels.

Animals↗
PubMed1981

Purification and pharmacological properties of eight sea anemone toxins from Anemonia sulcata, Anthopleura xanthogrammica, Stoichactis giganteus, and Actinodendron plumosum.

Eight different polypeptide toxins from sea anemones of four different origins (Anemonia sulcata, Anthopleura xanthogrammica, Stoichactis giganteus, and Actinodendron plumosum) have been studied. Three of these toxins are new; the purification procedure for the five other ones has been improved. Sea anemone toxins were assayed (i) for their toxicity to crabs and mice, (ii) for their affinity for the specific sea anemone toxin receptor situated on the Na+ channels of rat brain synaptosomes, and (iii) for their capacity to increase, in synergy with veratridine, the rate of 22Na+ entry into neuroblastoma cells via the Na+ channel. Some of the toxins are more active on crustaceans, whereas others are more toxic to mammals. A very good correlation exists between the toxic activity to mice, the affinity of the toxin for the Na+ channel in rat brain synaptosomes, and the stimulating effect on 22 Na+ uptake by neuroblastoma cells. The observation has also been made that the most cationic toxins are also the most active on mammals and the least active on crustaceans. Toxicities (LD50) to mice of the most active sea anemone toxins and of the most active scorpion toxins are similar, and sea anemone toxins at high enough concentrations prevent binding of scorpion toxins to their receptor. However, scorpion toxins have affinities for the Na+ channel which are approximately 60 times higher than those found for the most active sea anemone toxins. Three sea anemone toxins appear to be more interesting than toxin II from A. sulcata (the "classical" sea anemone toxin) for studies of the Na+ channel structure and mechanism when the source of the channel is of a mammalian origin. Two of these three toxins can be radiolabeled with iodine while retaining their toxic activity; they appear to be useful tools for future biochemical studies of the Na+ channel.

Animals↗
PubMed1981

Structure-function relationships of sea anemone toxin II from Anemonia sulcata.

Chemical modifications of sea anemone toxin II from Anemonia sulcata have been used to study the residues involved in its toxic action on crabs and mice and in its binding properties to the Na+ channel of rat brain synaptosomes. Guanidination of th epsilon-amino groups of lysines 35, 36, and 46 with O-methylisourea hydrogen sulfate did not change the net charge of the toxin molecule and had no effect upon its toxic and binding properties. Either acetylation or fluorescamine treatment of the toxin that destroyed the positive charges of the three epsilon-amino groups and of the alpha-amino function of Gly produced an almost complete loss of toxicity and a considerable decrease in the binding activity. Iodination of the toxin on His induced practically no loss of toxic or binding properties. Carbethoxylation of both histidines 32 and 37 with diethyl pyrocarbonate provoked an important decrease of both the toxicity and the binding activity. Modifications of the guanidine side chain of Arg with 1,2-cyclohexanedione fully destroyed both toxicity and binding of the toxin to the Na+ channel. Modification of the carboxylate functions of Asp, Asp, and of the COOH-terminal Gln with glycine ethyl ester in the presence of a soluble carbodiimide completely abolished the toxicity but left the affinity for the sea anemone toxin receptor unchanged. The antagonist character of this carboxylate-modified derivative was further confirmed by electrophysiological and Na+ flux experiments. The theoretical and practical significance of these results are discussed.

Acetic Anhydrides↗
PubMed1979

The sodium channel in non-impulsive cells. Interaction with specific neurotoxins.

The cell line C9 used in this paper has a resting potential of --50 mV (+/- 10 mV) but is unable to generate an action potential upon electrical stimulation. The cell membrane has receptors for the selectivity filter toxin tetrodotoxin as well as for the gating system toxins, veratridine, scorpion toxin and sea anemone toxin. The Na+ channel which remains silent to electrical stimulation in the absence of toxins can be chemically activated by the gating system toxins. This has been demonstarted by electrophysiological techniques and by 22Na+ flux studies. The electrophysiological approach has shown that the sea anemone toxin is able to induce a spontaneous slow-wave activity inhibited by tetrodotoxin. 22Na+ influx analyses have shown that veratridine and the sea anemone toxin produce an important increase of the initial rate of 22Na+ influx into the C9 cell. The stimulation of 22Na+ entry by these gating system toxins is similar to that found using spiking neuroblastoma cells. Veratridine and the sea anemone toxin on one hand as well as veratridine and the scorpion toxin on the other hand are synergistic in their action to stabilize an open and highly permeable form of the sodium channel. Stimulation of 22Na+ entry into the cell through the sodium channel maintained open by the gating system neurotoxins is completely suppressed by tetrodotoxin.

Animals↗