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At least 307 records · Page 17Linked to original sources
PubMed1995

Effect of scorpion toxin from Tityus serrulatus on the contraction of the isolated rat uterus.

Scorpion toxin T1 from Tityus serrulatus was tested for its effects on the isolated rat uterus preparation. T1 (5 micrograms/ml) caused a contraction of the uterus, which was potentiated by neostigmine (1.64 x 10(-6) M) and abolished by atropine (1.4 x 10(-7) M). After addition of neostigmine to the bath, we noted a higher amplitude of the toxin-induced contractions, and the appearance of repetitive rhythmic contractions. The scorpion toxin-induced contraction was not prevented by previous addition to the bath of hexamethonium or bradykinin, 5-HT and angiotensin II antagonists. The uterine contraction was prevented by previous addition to the bath of either tetrodotoxin (5 x 10(-8) M) or lidocaine (4.2 x 10(-5) M). These data seem to indicate that scorpion toxin-induced rat uterus contractions are due to actions on post-ganglionic autonomic nerve endings, with acetylcholine release and stimulation of muscarinic receptors.

Acetylcholine↗
PubMed1994

Isolation of a toxin from Centruroides infamatus infamatus Koch scorpion venom that modifies Na+ permeability on chick dorsal root ganglion cells.

A novel toxin was isolated and characterized from the venom of the Mexican scorpion Centruroides infamatus infamatus. It has an apparent mol. wt of 7600, compatible with the presence of 66 amino acid residues per molecule. The N-terminal amino acid sequence was determined (up to residue 48) and showed approximately 95% similarity with toxins from other Mexican scorpions of the gnus Centruroides. Experiments conducted with chick dorsal root ganglion cells showed that toxin 1 is a Na+ channel effector, causing a decrease in the peak Na+ permeability, similar to decreases observed for typical beta-scorpion toxins.

Amino Acid Sequence↗
PubMed1996

Interleukin-6 release following scorpion sting in children.

Interleukin-6 levels were measured in the serum of ten children following severe scorpion envenomation. Measurements were taken on arrival, at the emergency room, and 12 and 24 hr after arrival. Interleukin-6 was markedly elevated in the serum of eight out of ten children on arrival. Interleukin-6 levels gradually decreased toward normal values on 12 and 24 hr measurements, but remained above control levels on all measurements. These results imply that signs and symptoms following scorpion envenomation may in part be explained by release of cytokines. Human and experimental animal studies are required in order to verify the assumption that interleukin-6 and other cytokines are involved in the pathogenesis of scorpion envenomation.

Animals↗
PubMed2005

Proteomic analysis of the venom and characterization of toxins specific for Na+ - and K+ -channels from the Colombian scorpion Tityus pachyurus.

The Colombian scorpion Tityus pachyurus is toxic to humans and is capable of producing fatal accidents, but nothing is known about its venom components. This communication reports the separation of at least 57 fractions from the venom by high performance liquid chromatography. From these, at least 104 distinct molecular weight compounds were identified by mass spectrometry analysis. The complete amino acid sequences of three peptides were determined and the partial sequences of three others were also identified. Electrophysiological experiments conducted with ion-channels expressed heterologously on Sf9 cells showed the presence of a potent Shaker B K(+)-channel blocker. This peptide (trivial name Tpa1) contains 23 amino acid residues closely packed by three disulfide bridges with a molecular mass of 2,457 atomic mass units. It is the third member of the sub-family 13, for which the systematic name is proposed to be alpha-KTx13.3. The mice assay showed clearly the presence of toxic peptides to mammals. One of them named Tpa2, containing 65 amino acid residues with molecular mass of 7,522.5 atomic mass units, is stabilized by four disulfide bridges. It was shown to modify the Na(+)-currents of F-11 and TE671 cells in culture, similar to the beta scorpion toxins. These results demonstrate the presence of toxic peptides in the venom of T. pachyurus and confirm that accidents with this species of scorpion should be considered an important human hazard in Colombia.

Amino Acid Sequence↗
PubMed2004

Proteomics of the venom from the Amazonian scorpion Tityus cambridgei and the role of prolines on mass spectrometry analysis of toxins.

Scorpion venom are complex mixtures of peptides, known to cause impairment of ion-channel function in biological membranes. This report describes the separation of approximately 60 different components by high performance liquid chromatography and the characterization by Edman degradation and mass spectrometry of 26 peptides from the soluble venom of the Amazonian scorpion Tityus cambridgei. One of these peptides, named Tc48a, was fully characterized. It contains 65 amino acid residues, the C-terminal residue is amidated and it affects Na(+)-channels with a K(d) of about 82 nM. Furthermore, this report shows the thermo-instability of scorpion toxins subjected to electron spray ionization-mass spectrometry (ESI-MS). When a proline residue is located near the N-terminal region of the toxin, not stabilized by disulfide bridges, artificial components are generated by the mass spectrometer conditions, due to the cleavage of the peptide bond at the proline positions. This phenomenon was confirmed by using four model proteins (variable regions of immunoglobulins) studied by ESI-MS and matrix assisted laser desorption ionization-time of flight (MALDI-TOF)/MS.

Amino Acid Sequence↗
PubMed2005

Screening of plants acting against Heterometrus laoticus scorpion venom activity on fibroblast cell lysis.

The aqueous extracts of 64 plant species, listed as animal- or insect-bite antidotes in old Thai drug recipes were screened for their activity against fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The venom was preincubated with plant extract for 30 min and furthered treated to confluent fibroblast cells for 30 min. More than 40% efficiency (test/control) was obtained from cell treatment with venom preincubated with extracts of Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn. (Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae), Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk (Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L. (Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC. (Sapindaceae), indicating that they had a tendency to be scorpion venom antidotes. However, only Andrographis paniculata and Barringtonia acutangula extracts provided around 50% viable cells from extract treatments without venom preincubation. These two plant extracts are expected to be scorpion venom antidotes with low cytotoxicity.

Animals↗
PubMed2004

Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins.

Non-proline cis peptide bonds have been observed in numerous protein crystal structures even though the energetic barrier to this conformation is significant and no non-prolyl-cis/trans-isomerase has been identified to date. While some external factors, such as metal binding or co-factor interaction, have been identified that appear to induce cis/trans isomerization of non-proline peptide bonds, the intrinsic structural basis for their existence and the mechanism governing cis/trans isomerization in proteins remains poorly understood. Here, we report the crystal structure of a newly isolated neurotoxin, the scorpion alpha-like toxin Buthus martensii Karsch (BmK) M7, at 1.4A resolution. BmK M7 crystallizes as a dimer in which the identical non-proline peptide bond between residues 9 and 10 exists either in the cis conformation or as a mixture of cis and trans conformations in either monomer. We also determined the crystal structures of several mutants of BmK M1, a representative scorpion alpha-like toxin that contains an identical non-proline cis peptide bond as that observed in BmK M7, in which residues within or neighboring the cis peptide bond were altered. Substitution of an aspartic acid residue for lysine at residue 8 in the BmK M1 (K8D) mutant converted the cis form of the non-proline peptide bond 9-10 into the trans form, revealing an intramolecular switch for cis-to-trans isomerization. Cis/trans interconversion of the switch residue at position 8 appears to be sequence-dependent as the peptide bond between residues 9 and 10 retains its wild-type cis conformation in the BmK M1 (K8Q) mutant structure. The structural interconversion of the isomeric states of the BmK M1 non-proline cis peptide bond may relate to the conversion of the scorpion alpha-toxins subgroups.

Amino Acid Sequence↗
PubMed2006

X-ray structure and mutagenesis of the scorpion depressant toxin LqhIT2 reveals key determinants crucial for activity and anti-insect selectivity.

Scorpion depressant beta-toxins show high preference for insect voltage-gated sodium channels (Na(v)s) and modulate their activation. Although their pharmacological and physiological effects were described, their three-dimensional structure and bioactive surface have never been determined. We utilized an efficient system for expression of the depressant toxin LqhIT2 (from Leiurus quinquestriatushebraeus), mutagenized its entire exterior, and determined its X-ray structure at 1.2 A resolution. The toxin molecule is composed of a conserved cysteine-stabilized alpha/beta-core (core-globule), and perpendicular to it an entity constituted from the N and C-terminal regions (NC-globule). The surface topology and overall hydrophobicity of the groove between the core and NC-globules (N-groove) is important for toxin activity and plays a role in selectivity to insect Na(v)s. The N-groove is flanked by Glu24 and Tyr28, which belong to the "pharmacophore" of scorpion beta-toxins, and by the side-chains of Trp53 and Asn58 that are important for receptor site recognition. Substitution of Ala13 by Trp in the N-groove uncoupled activity from binding, suggesting that this region of the molecule is also involved in "voltage-sensor trapping", the mode of action that typifies scorpion beta-toxins. The involvement of the N-groove in recognition of the receptor site, which seems to require a defined topology, as well as in sensor trapping, which involves interaction with a moving channel region, is puzzling. On the basis of the mutagenesis studies we hypothesize that following binding to the receptor site, the toxin undergoes a conformational change at the N-groove region that facilitates the trapping of the voltage-sensor in its activated position.

Animals↗
PubMed2004

Molecular cloning and functional expression of the alpha-scorpion toxin BotIII: pivotal role of the C-terminal region for its interaction with voltage-dependent sodium channels.

Alpha scorpion toxins bind to receptor site 3 on voltage-dependent sodium channels and inhibit their inactivation. The alpha-scorpion toxin BotIII is the most toxic protein of Buthus occitanus tunetanus. Its sequence differs only by three amino acid residues from that of AahII, the most active alpha-toxin. Due to their high affinity and selectivity for mammalian sodium channels, BotIII and AahII represent powerful tools for studying the molecular determinants of specificity for voltage-dependent sodium channels. Sequence analysis of BotIII gene has revealed two exons separated by a 381-bp intron and a signal peptide of 19 amino acids. We succeeded in expressing BotIII in significantly higher amounts than AahII the only expressed strict alpha anti-mammalian scorpion toxin reported in the literature. We have also modified specific amino acid residues of BotIII. The recombinant and the natural toxins differ by the amidation of the C-terminal residue. Toxicity and binding experiments indicated: (a) the affinity of rBotIII-OH and rAahII-OH (rBotIII-OH with the 3 mutations R10V, V51L, N64H) for the voltage-dependent sodium channels is reduced compared to the natural toxins. This data revealed the important role of the C-terminal amidation for the biological activity of BotIII and AahII; (b) the single mutation N64H is responsible for the difference of toxicity and affinity between rBotIII-OH and rAahII-OH; (c) the addition of the sequence GR to rBotIII-OH leads to the loss of biological activity. This study is in agreement with the important role attributed to the C-terminal sequence of alpha-toxins in their interaction with sodium channels receptors.

Amino Acid Sequence↗
PubMed2004

Purification, characterization and sequence determination of BmKK4, a novel potassium channel blocker from Chinese scorpion Buthus martensi Karsch.

The scorpion neurotoxin BmKK4 was purified from the venom of the Chinese scorpion Buthus martensi Karsch by a combination of gel-filtration, ion exchange and reversed phase chromatography. The primary sequence of BmKK4 was determined using the tandem MS/MS technique and the cDNA database searching as followings: ZTQCQ SVRDC QQYCL TPDRC SYGTC YCKTT (NH(2)). BmKK4 is the first isolated member of a new subfamily alpha-KTx17 of scorpion K(+) toxins.

Amino Acid Sequence↗
PubMed2004

Current views on scorpion toxins specific for K+-channels.

Much of our knowledge on K+-channels was elucidated using specific peptide ligands isolated from a number of venomous organisms. Recently, this field received a strong support and increased interest due to the solution of the three-dimensional structure of a couple of K+-channels. At the same time, several new subfamilies of specific toxins for K+-channels were isolated from scorpion venoms, enhancing the availability and diversity of such useful molecular tools. It opened new lines of research for the better understanding of K+-channel biophysics and pharmacology. In this review, we listed 120 amino acid sequences of peptides isolated from scorpion venoms. They were demonstrated or assumed to be specific for K+-channels. These sequences were aligned and used to generate a rooted phylogenetic tree. The evolutionary tree indicates that several clusters of divergent peptides show preference for specific subtypes of channels. The three-dimensional structures of representative examples of these peptides were drawn and analysed concerning the molecular fitness of their interactions with the channel targets. Four different interacting modes were identified to exist between scorpion toxins and the various subtypes of K+-channels.

Amino Acid Sequence↗
PubMed2004

The Brazilian scorpion Tityus costatus Karsch: genes, peptides and function.

The venom of the scorpion Tityus costatus contains peptides toxic to humans but scarce information on their structure and function is available. Here, we report the separation of 50 different components by high performance liquid chromatography and the identification of approximately 90 distinct components by mass spectrometry analysis, with molecular weights varying from 413 to 45482 atomic mass units. Four peptides were fully sequenced: (i) a butantoxin-like peptide that blocks Shaker K+ channel; (ii) an insect toxin-like peptide; (iii) a scorpine-like peptide, and a short heptapeptide of unknown function. Fifteen peptides were directly sequenced at the N-terminal region, among which are components toxic to mice. A cDNA library was constructed and 13 clones were isolated and sequenced. Some of these peptides and genes are similar to other known scorpion toxins. Based on these results, stings by scorpions of the species Tityus costatus should be taken with caution by medical doctors.

Amino Acid Sequence↗
PubMed2006

HgeTx1, the first K+-channel specific toxin characterized from the venom of the scorpion Hadrurus gertschi Soleglad.

A novel toxin was identified, purified and characterized from the venom of the Mexican scorpion Hadrurus gertschi (abbreviated HgeTx1). It has a molecular mass of 3950 atomic mass units (a.m.u.) and contains 36 amino acids with four disulfide bridges established between Cys1-Cys5, Cys2-Cys6, Cys3-Cys7 and Cys4-Cys8. It blocks reversibly the Shaker B K(+)-channels with a Kd of 52nM. HgeTx1 shares 60%, 45% and 40% sequence identity, respectively, with Heterometrus spinnifer toxin1 (HsTX1), Scorpio maurus K(+)-toxin (maurotoxin) and Pandinus imperator toxin1 (Pi1), all four-disulfide bridged toxins. It is 57-58% identical with the other scorpion K(+)-channel toxins that contain only three disulfide bridges. Sequence comparison, chain length and number of disulfide bridges analysis classify HgeTx1 into subfamily 6 of the alpha-KTx scorpion toxins (systematic name: alpha-KTx 6.14).

Amino Acid Sequence↗
PubMed2004

Scorpion envenoming in two regions of Colombia: clinical, epidemiological and therapeutic aspects.

To determine clinical and epidemiological features of scorpion stings in two departments of Colombia, a descriptive study was performed in the hospitals of 10 towns from Antioquia (2 256 071 inhabitants) and five from Tolima (630 424 inhabitants). One hundred and twenty-nine cases were admitted during one year, 51 in Antioquia, 78 in Tolima and 41 were children less than 15 years old. Most stings (70.5%) occurred inside the house; 27.9% were on the hands and 26.4% on the feet. The scorpion species involved were Tityus pachyurus (51), Centruroides gracilis (31), T. fuehrmanni (29), T. asthenes (7) and Chactas spp. (1). In 10 cases the scorpion involved was not identified. Systemic envenoming signs (e.g. vomiting, tachypnea) were significantly more frequent in children than in adults (P < 0.05). Four children had hypertension, but none developed pulmonary oedema. One 3-year-old girl, stung by T. asthenes, had acute oedematous pancreatitis. Ninety-eight patients had mild envenoming. Moderate (27 patients) and severe (four patients) envenoming was significantly more frequent in children than in adults (P = 0.003; relative risk = 2.97). A pepsin-digested anti-Centruroides spp. antivenom was administered to 19 of 31 patients presenting systemic envenoming signs. No adverse reactions to antivenom were observed.

Adolescent↗
PubMed2005

Immunology of scorpion toxins and perspectives for generation of anti-venom vaccines.

Scorpions and other venomous animals contain concentrates of biologically active substances developed to block vital physiological and biochemical functions of the victims. These have contrasting human health concerns, provide important pharmacological raw material and pose a serious threat to human life and health in tropical and subtropical regions. Because only occasional and minor quantities of venom are introduced into the human organism with a scorpion sting and their mortal effect is an acute phenomenon these substances are unknown to the immune defense system and thus no immunity has appeared against them during evolution. Antidotes prepared from animal anti-sera are effective against some species of scorpions but depend on the manufacturer and the availability of product to the medical community. Although significant progress has been made in immunological studies of certain groups of toxins, few centers are dedicated to this research. Information is still insufficient to generate a comprehensive picture of the subject and to propose vaccines against venoms. A novel approach based on mimotopes selected from phage-displayed random peptide libraries show potential to impel further progress of toxin immunological studies and to provide putative vaccine resources. In this report we revise the "state of the art" in the field.

Animals↗
PubMed2003

BTK-2, a new inhibitor of the Kv1.1 potassium channel purified from Indian scorpion Buthus tamulus.

A novel inhibitor of voltage-gated potassium channel was isolated and purified to homogeneity from the venom of the red scorpion Buthus tamulus. The primary sequence of this toxin, named BTK-2, as determined by peptide sequencing shows that it has 32 amino acid residues with six conserved cysteines. The molecular weight of the toxin was found to be 3452 Da. It was found to block the human potassium channel hKv1.1 (IC(50)=4.6 microM). BTK-2 shows 40-70% sequence similarity to the family of the short-chain toxins that specifically block potassium channels. Multiple sequence alignment helps to categorize the toxin in the ninth subfamily of the K+ channel blockers. The modeled structure of BTK-2 shows an alpha/beta scaffold similar to those of the other short scorpion toxins. Comparative analysis of the structure with those of the other toxins helps to identify the possible structure-function relationship that leads to the difference in the specificity of BTK-2 from that of the other scorpion toxins. The toxin can also be used to study the assembly of the hKv1.1 channel.

Amino Acid Sequence↗
PubMed1997

Genomic organization of the KTX2 gene, encoding a 'short' scorpion toxin active on K+ channels.

A single intron of 87 bp, close to the region encoding the C-terminal part of the signal peptide, was found in the gene of the 'short' scorpion toxin kaliotoxin 2 of Androctonus australis acting on various types of K+ channels. Its A+T content was particularly high (up to 86%). By walking and ligation-mediated PCR, the promoter sequences of the kaliotoxin 2 gene of Androctonus australis were studied. The transcription unit of the gene is 390 bp long. Consensus sequences were identified. The genes of 'short' scorpion toxins active on K+ channels are organized similarly to those of the 'long' scorpion toxins active on Na+ channels and not like those of structurally related insect defensins, which are intronless.

Amino Acid Sequence↗
PubMed1995

Solution structure of an Old World-like neurotoxin from the venom of the New World scorpion Centruroides sculpturatus Ewing.

We have determined the solution structure of an alpha-toxin, CsE-V, isolated from the venom of the New World scorpion Centruroides sculpturatus Ewing (CsE). This toxin causes spontaneous rhythmic contractions in muscle. Unlike other New World toxins from CsE, this protein exhibits amino acid insertions and deletions at locations similar to Old World toxins and may thus represent a transition protein between the New World and Old World scorpion alpha-toxins. Sequence-specific assignments were made using 600 MHz 1H two-dimensional NMR data. NOESY, PH-COSY and amide-exchange data were used to deduce constraints for molecular modeling calculations. Distance geometry and dynamical simulated annealing calculations were performed to generate a family of 70 structures free of constraint violations. With respect to this family of structures, the energy-minimized average structure had root-mean-square deviations of 0.74 and 1.32 A for backbone and all atoms, respectively (excluding the C-terminal dipeptide, which is disordered). As with other scorpion toxins, the secondary structure of CsE-V consists of an alpha-helix, a three-strand anti-parallel beta-sheet, four beta-turns, and a hydrophobic patch that includes tyrosine residues in herringbone configuration. Unlike the CsE-v3 and -v1 proteins from C. sculpturatus, all of the proline residues were found to be in the trans configuration. The alpha-helix is slightly longer in CsE-V. The overall structure is more similar to the Old World alpha-toxin AaH-II from Androctonus australis Hector (r.m.s.d 1.59 A for backbone atoms of matching residues) than to the New World alpha-toxin CsE-v3 (r.m.s.d. 1.91 A). These structural data on CsE-V add further to our knowledge of the conformational repertoire exhibited by these sodium channel-binding neurotoxins.

Amino Acid Sequence↗