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PubMed2006

Immunocytochemical localization of scorpion digestive lipase.

The scorpion hepatopancreas consists of digestive diverticula and interstitial tissue. A digestive diverticulum is composed of two differentiated cell types: the secretory zymogene-like cells and the digestive cells which are the most abundant. The scorpion digestive lipase (SDL) has been previously purified from scorpion hepatopancreas, but its cellular localization has not yet been established. Polyclonal antibodies specific to SDL were prepared and used in immunofluorescence and immunogold techniques to determine the cellular location of SDL. Our results clearly established that SDL was detected intracellularly in specific vesicles tentatively named (SDL+) granules of the digestive cells. No immunolabelling was observed in secretory zymogene-like cells. This immunocytolocalization indicates that lipid digestion might occur in specific granules inside the digestive cells, as suggested by previous studies on the scorpion digestive process.

Animals↗
PubMed2004

Isolation and molecular characterization of LVP1 lipolysis activating peptide from scorpion Buthus occitanus tunetanus.

LVP1, a novel protein inducing lipolytic response in adipose cells, was purified from scorpion Buthus occitanus tunetanus venom. It represented 1% of crude venom proteins, with pHi approximately 6 and molecular mass of 16170 Da. In contrast to well-characterized scorpion toxins, reduction and alkylation of LVP1 revealed an heterodimeric structure. Isolated alpha and beta chains of LVP1 have a respective molecular mass of 8877 and 8807 Da as determined by mass spectrometry. The N-terminal and some internal peptide sequences of LVP1alpha and beta were determined by Edman degradation. The full amino acid sequences of both chains were deduced from nucleotide sequences of the corresponding cDNAs prepared based on peptide sequences and the 3' and 5' RACE methodologies. LVP1alpha and beta cDNAs encode a signal peptide of 22 residues and a mature peptide of 69 and 73 residues, respectively. Each mature peptide contains seven cysteines, which are compatible with an interchain disulfide bridge. The cDNA deduced protein structures share a high similarity with those of some Na+ channel scorpion toxins. LVP1 was not toxic to mice after intracerebro-ventricular injection. LVP1 stimulated lipolysis on freshly dissociated rat adipocytes in a dose-dependent manner with EC50 of approximately 1+0.5 microg/ml. LVP1 subunits did not display any lipolytic activity. As previously described for venom, beta adrenergic receptor (beta AR) antagonists interfere with LVP1 activity. Furthermore, it is shown that LVP1 competes with [3H]-CGP 12177 (beta1/beta2 antagonist) for binding to adipocyte plasma membrane with an IC50 of about 10(-7) M. These results demonstrate the existence of a new type of scorpion venom nontoxic peptides that are structurally related to Na+ channel toxins but can exert a distinct biological activity on adipocyte lipolysis through a beta-type adrenoreceptor pathway.

Adipocytes↗
PubMed2005

Neurohormonal activation in severe scorpion envenomation: correlation with hemodynamics and circulating toxin.

We studied the effects of scorpion (Androctonus australis hector) venom on hemodynamics and on the release of catecholamines, neuropeptide Y (NPY), endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in dog model of severe scorpion envenomation. Nine mongrel anesthetized dogs were submitted to mechanical ventilation through intubation and were administered intravenously purified dried scorpion venom (Androctonus autstralis) 0.05 mg/kg. Measurements including pulmonary artery catheter derived parameters, serum toxin levels and humoral variables were performed at baseline (before venom injection) and 5, 15, 30 and 60 min after venom injection. Humoral variables included: serum lactate, epinephrine (EP), norepinephrine (NE), NPY, ET-1 and ANP plasma concentrations. Scorpion venom caused rapid and transient increase of mean arterial pressure (MAP) and PAOP associated with a marked and sustained decline in cardiac output (-55% at 60 min; P < 0.001). Hemodynamic changes were associated with a rapid and significant increase of all measured hormones. The highest increase was for NE (28-fold) and EP (25-fold). MAP was closely correlated with NE and less significantly correlated with toxin levels. Similarly, significant correlation was observed between PAPO and ANP plasma levels. These findings support the implication of excessive catecholamines release in hemodynamic disturbances of severe SE and suggest that NPY and ET-1 could be involved in this process. Serum toxin does not appear to consistently contribute to these effects. Through its correlation with PAOP, ANP could be a reliable and useful marker of cardiac dysfunction in SE.

Animals↗
PubMed1999

Molecular cloning and sequencing of two 'short chain' and two 'long chain' K(+) channel-blocking peptides from the Chinese scorpion Buthus martensii Karsch.

Five full-length cDNAs encoding the precursors of two 'short chain' scorpion non-toxic peptides active on Ca(2+)-activated K(+) channels (BmP02 and BmP03) and two novel putative long chain K(+) channel-blocking peptides (named BmTXKbeta and BmTXKbeta2) were first isolated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch (BmK). BmTXKbeta2 showed a high similarity with AaTXKbeta, while BmTXKbeta was completely different in the deduced primary structure from the long chain and short chain scorpion toxins already characterized. Thus, BmTXKbeta expands the scorpion long chain K(+) channel-blocking peptide family. Although little sequence similarity exists between the above two short and two long peptides, they are similar at the positions of six cysteines, suggesting that they should all share a similar scaffold composed of an alpha-helix and a three-stranded beta-sheet.

3' Untranslated Regions↗
PubMed2003

Dysregulation of apoptosis in scorpion envenomed children: its reflection on their outcome.

In the present study, 46 children in Upper Egypt (less than 13 years old) were admitted to the Pediatric Intensive Care Unit for scorpion envenomation. They were compared with 20 apparently healthy children of matching age and sex as controls. Out of the studied victims, 25 children (54%) showed signs of severe envenomation and multiple organ dysfunction (MOD), while 21 victims (46%) showed signs of mild envenomation. The serum levels of apoptotic markers, soluble Fas (sFas), soluble Fas ligand (sFasL) and Bcl-2, were determined for both victims and controls. In addition, the serum levels of nitric oxide (NO) and lipid peroxides (LPO) were also measured. Scoring of MOD was evaluated using Logistic Organ Dysfunction System Score (LODS) for the severely envenomed victims. All victims (both severe and mild cases) showed significantly higher mean levels of sFas, LPO and NO and significantly lower serum levels of Bcl-2 in comparison to the controls. The level of sFasL was not detectable in the sera of the healthy control group. The case fatality rate was 15%. The severely envenomed children with MOD as well as the non-survivors showed significantly higher serum levels of sFas, sFasL, LPO and NO and significantly lower serum levels of Bcl-2 in comparison to the mild envenomed victims and the surviving victims of severe cases, respectively. The LODS score of the severely envenomed victims showed significant positive correlations with sFas and LPO and significant negative correlation with Bcl-2. In all victims, a significant positive correlation was detected between sFas and NO. On the other hand, Bcl-2 was significantly negatively correlated with both sFas and LPO. In conclusion, our study revealed that scorpion envenomation can increase apoptosis as shown by up-regulation of sFas/sFasL system and down-regulation of Bcl-2 that was associated by elevation of LPO and NO. This dysregulation of apoptosis was increased with the severity of scorpion envenomation and its extent increased as MOD score and outcome increased. Therefore, sFas and Bcl-2 may be of value in predicting the outcome of these cases. The increase of the extent of apoptosis detected in this study seems to play a role in the outcome of scorpion envenomation, and hence, should be taken into consideration for strategies of therapeutic regimen.

Animals↗
PubMed2003

New insight on scorpion divergence inferred from comparative analysis of toxin structure, pharmacology and distribution.

The divergence of Buthidae, the most abundant family of scorpions, has relied thus far on anatomical and morphological features, but still remains controversial. However, much information has accumulated on Buthidae long-chain scorpion toxins affecting neuronal sodium channel conductance (alpha- and beta-toxins) and their pharmacology. Therefore, we constructed a toxin evolutionary tree, which together with recent data on toxin gene organization, toxin structures, and worldwide dispersion, sheds light on toxin and hence, scorpion divergence. Based on these data, we suggest that in the ancient world, the ancestral long-chain toxins affecting sodium channels developed into beta-like toxins, which most likely developed into alpha- and beta-toxins before the separation of South America from Africa. Subsequently, in the Old World, mostly excitatory and depressant toxins developed from the ancestral beta-like toxin and in the New World a new type of toxin group with beta-toxin structure but alpha-toxin activity developed from the beta-toxins. Assisted by the worldwide distribution of toxins and the zoogeographical dispersion of the studied genera in Asia and Africa (Old World) and in South and North America (New World), we suggest a route of divergence for some of the Buthidae scorpions, a task that has reached a standstill when morphological and anatomical features were used.

Amino Acid Sequence↗
PubMed1999

Molecular characterization of a new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensi Karsch.

Besides the neurotoxins active on mammals, a new excitatory insect selective toxin with a mice analgesic activity was found and purified from the venom of the scorpion Buthus martensi Karsch (BmK) (Ji, Y.H., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Hsu, K., Rochat, H., 1996. Toxicon 34, 987; Luo, M.J., Xiong, Y.M., Wang, M., Wang, D.C., Chi, C.W., 1997. Toxicon 35, 723.). This peptide (designated as BmK IT-AP) is composed of 72 amino acid residues. Its primary structure was determined by automated Edman degradation of the N-terminal part of the reduced and S-carboxamidemethylated protein and its lysylendopeptidase degraded fragments. Based on the determined sequence, the gene specific primers were designed and synthesized for 3' and 5' RACE (rapid amplification of cDNA ends). Their partial cDNA fragments obtained by 3' and 5' RACEwere cloned and sequenced and the full length cDNA sequence of BmK IT-AP was then completed by overlapping their two partial cDNA sequences. It encodes a precursor of 90 amino acid residues: a signal peptide of 18 residues and a mature peptide of 72 residues which are consistent with the determined protein sequence of BmK IT-AP. The genomic DNA of the peptide was also amplified by PCR from the scorpion genomic DNA and sequenced, which is a first report on the genomic structure of a scorpion toxin specific for insects. Its sequence revealed an intron of 590 bp inserted in the end part of the signal peptide. The peptide caused a fast excitatory contraction paralysis on house fly larvae. Furthermore, the peptide also showed an obvious analgesic effect on mice, as assayed by using a twisting test model. This effect of BmK IT-AP well characterized at molecular level is first reported among the known scorpion insect neurotoxins.

Amino Acid Sequence↗
PubMed2000

Acid-base balance following Tityus serrulatus scorpion envenoming in anaesthetized rats.

In the present work the pH and arterial blood gases were measured in fasted and fed male albino rats, weighing 297 +/- 13 g, anaesthetized with urethane (1.4 g/kg, i.p.) before and after injection of T1 fraction from Titys serrulatus scorpion venom, during 60 min. Arterial blood samples were collected at 0, 5, 15, 30 and 60 min for pH, pCO2, pO2, bicarbonate and base-excess analysis. The data showed that the scorpion toxin induced a continuous drop in the blood pH along the time. Hypercapnia and hypoxemia peaking at 30 min and followed by a recovery towards normal values at 60 min were also observed. A pronounced decrease in the blood bicarbonate levels at 60 min and negative base-excess values along with time were evident at 60 min. The comparisons between fasted and fed animals have shown that in the last group the effects of scorpion toxin on the arterial blood gases were less pronounced. We conclude that T1 fraction of Tityus serrulatus scorpion venom induces in anaesthetized rats an acute respiratory acidosis followed by metabolic acidosis.

Acid-Base Equilibrium↗
PubMed2005

A spider toxin that induces a typical effect of scorpion alpha-toxins but competes with beta-toxins on binding to insect sodium channels.

Delta-palutoxins from the spider Paracoelotes luctuosus (Araneae: Amaurobiidae) are 36-37 residue long peptides that show preference for insect sodium channels (NaChs) and modulate their function. Although they slow NaCh inactivation in a fashion similar to that of receptor site 3 modifiers, such as scorpion alpha-toxins, they actually bind with high affinity to the topologically distinct receptor site 4 of scorpion beta-toxins. To resolve this riddle, we scanned by Ala mutagenesis the surface of delta-PaluIT2, a delta-palutoxin variant with the highest affinity for insect NaChs, and compared it to the bioactive surface of a scorpion beta-toxin. We found three regions on the surface of delta-PaluIT2 important for activity: the first consists of Tyr-22 and Tyr-30 (aromatic), Ser-24 and Met-28 (polar), and Arg-8, Arg-26, Arg-32, and Arg-34 (basic) residues; the second is made of Trp-12; and the third is made of Asp-19, whose substitution by Ala uncoupled the binding from toxicity to lepidopteran larvae. Although spider delta-palutoxins and scorpion beta-toxins have developed from different ancestors, they show some commonality in their bioactive surfaces, which may explain their ability to compete for an identical receptor (site 4) on voltage-gated NaChs. Yet, their different mode of channel modulation provides a novel perspective about the structural relatedness of receptor sites 3 and 4, which until now have been considered topologically distinct.

Alanine↗
PubMed1996

Transfer of a beta-hairpin from the functional site of snake curaremimetic toxins to the alpha/beta scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein.

The alpha/beta scorpion fold is shared by scorpion toxins, insect defensins, and plant thionins. This small and functionally versatile template contains an alpha-helix and a triple beta-sheet linked by three disulfide bridges. With the view to introduce novel functional centers within this fold, we replaced the sequence (the cysteines and glycines excepted) of the original beta-hairpin of a scorpion toxin by the sequence of a beta-hairpin that forms part of the site by which snake neurotoxins bind to nicotinic acetylcholine receptors (AcChOR). The resulting chimeric protein, synthesized by chemical means, binds to AcChOR, though with a lower affinity than the snake toxins [Drakopoulou; E., Zinn-Justin, S., Guenneugues, M., Gilquin, B., Ménez, A., & Vita, C. (1996) J. Biol. Chem. 271, 11979-11987]. The work described in this paper is an attempt to clarify the structural consequences associated with the transfer of the beta-hairpin. We report the determination of the three-dimensional solution structure of the chimeric protein by proton NMR spectroscopy and molecular dynamics calculations. Comparison of the structure of the chimera with those of the scorpion alpha/beta toxin and of the snake neurotoxin shows that (i) the new protein folds as an alpha/beta motif and (ii) the beta-hairpins of the chimera and of the curaremimetic toxin adopt a similar conformation. A closer inspection of the differences between the structures of the original and transferred beta-hairpins allows rationalization of the biological properties of the chimera.

Amino Acid Sequence↗
PubMed1997

Effects of scorpion venom on central and peripheral circulatory response in an open-chest dog model.

Scorpion venom can induce in dogs severe haemodynamic changes leading to rapid rise in systemic blood pressure and cardiac output, followed by reduction of cardiac output and blood pressure within 1 h. The decrease in cardiac output is not related to myocardial dysfunction (Tarasiuk et al. 1994). We hypothesized that scorpion venom affects cardiac output by reducing venous return to the heart. Venous return was studied by steady-state measurements of cardiac output, the pressure gradient and resistance to venous return, in 16 dogs following injection of 0.05 mg kg-1 venom obtained from the scorpion species Leiurus quinquestriatus. In eight of the 16 dogs, atropine (0.1 mg kg-1) was given 15 min prior to venom injection (n = 4) or 85 min (n = 4) after venom administration. In five additional dogs, the stability of the preparation over time was evaluated following the same protocol without the injection of the venom. At 15 min, the venom induced an increase in blood pressure (80%) and cardiac output (250%) (P < 0.001) with little effect on heart rate. At 90 min, cardiac output and heart rate declined considerably below baseline (P < 0.001). Atropine prevented the decrease in heart rate, but did not affect the reduction of cardiac output. Five minutes after venom injection, mean circulatory pressure increased by 300% (P < 0.001), which was accompanied by a rightward shift of the venous return curve with no effect on resistance to venous return. At 120 min, mean circulatory pressure recovered and resistance to venous return remained at 40% (P < 0.01) above baseline. This study indicates that, in dogs, scorpion venom affects cardiac output by modifying the determinants of venous return. The initial increase in cardiac output is related to increased mean circulatory pressure since resistance to venous return did not change. The later fall in cardiac output is related to the reduction of mean circulatory pressure and increased resistance to venous return.

Animals↗
PubMed2002

Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa.

Two novel pore-forming peptides have been isolated from the venom of the South-African scorpion Opistophtalmus carinatus. These peptides, designated opistoporin 1 and 2, differ by only one amino acid and belong to a group of alpha-helical, cationic peptides. For the first time, a comparison of the primary structures of alpha-helical pore-forming peptides from scorpion venom was undertaken. This analysis revealed that peptides in the range of 40-50 amino acids contain a typical scorpion conserved sequence S(x)3KxWxS(x)5L. An extensive study of biological activity of synthesized opistoporin 1 and parabutoporin, a pore-forming peptide previously isolated from the venom of the South-African scorpion Parabuthus schlechteri, was undertaken to investigate an eventual cell-selective effect of the peptides. Opistoporin 1 and parabutoporin were most active in inhibiting growth of Gram-negative bacteria (1.3-25 micro m), while melittin and mastoparan, two well-known cytolytic peptides, were more effective against Gram-positive bacteria in the same concentration range. In addition, the peptides showed synergistic activity with some antibiotics commonly used in therapy. Opistoporin 1 and parabutoporin had hemolytic activity intermediate between the least potent mastoparan and the highly lytic melittin. Furthermore, all peptides inhibited growth of fungi. Experiments with SYTOX green suggested that this effect is related to membrane permeabilization.

Africa, Southern↗
PubMed1996

Tetrodotoxin reverses brevetoxin allosteric inhibition of scorpion alpha-toxin binding on rat brain sodium channels.

Voltage-sensitive sodium channels are responsible for the initiation of action potentials in many excitable cells. Several neurotoxins bind to distinct receptor sites on sodium channels and reveal strong allosteric interactions among them. Scorpion alpha toxins, which inhibit sodium channel inactivation by binding to receptor site 3, have been very important tools to study sodium channel structure and function. Recently, we have shown that brevetoxin induce a strong negative allosteric modulation on scorpion alpha-toxin binding on rat brain sodium channels, in contrast to previously published studies. In this report we have examined the reasons for this discrepancy and found new, unexpected allosteric interactions between the tetrodotoxin and brevetoxin receptor sites, using scorpion alpha-toxin as sensitive probe for subtle conformational changes on sodium channels. Tetrodotoxin reverses the negative modulation induced by brevetoxin on scorpion alpha-toxin binding, revealing new dynamic interactions in sodium channel structure.

Allosteric Site↗
PubMed2002

New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.

The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.

Amino Acid Sequence↗
PubMedDate not supplied

Ecophysiological adaptations to dry thermal environments measured in two unrestrained Namibian scorpions, Parabuthus villosus (Buthidae) and Opisthophthalmus flavescens (Scorpionidae).

The daily changes in body temperature experienced by Parabuthus villosus (Buthidae), a scorpion found on the gravel plains around Gobabeb, Namibia, and by Opisthophthalmus flavescens (Scorpionidae), a dune-dwelling species from the same area, were measured under similar field conditions. Thermocouples implanted under the segments of the mesosoma measured maximum temperatures as high as 43 degrees C in the shade. Air temperatures reached a maximum of 33 degrees C during the daytime and a minimum of 12 degrees C at night. Very low metabolic rates compared with those of other nonsedentary invertebrates were recorded in both species; oxygen consumption ranged from 8 microL g-1 h-1 at 16 degrees C to 115 microL g-1 h-1 at 40 degrees C. A pulsed Doppler system was used to measure heart rate in situ in free-moving scorpions. At night, heart rate declined to about 4 beats min-1 in resting undisturbed scorpions. During daylight excursions and while scorpions hunted for food, heart rates as high as 180 beats min-1 were observed. Heart rate was linearly correlated with temperature in P. villosus, with a slope of 2.37 (Q10 = 2.18), but in O. flavescens only a limited correlation was observed, with a slope of 1.18 (Q10 = 1.69). In O. flavescens, heart rate showed hysteresis as body temperature rose during daylight and then decreased during the late afternoon and evening; the reverse was observed in P. villosus. In both species, haemocyanin-oxygen affinity was independent of temperature, with a higher oxygen affinity and a larger pH sensitivity in O. flavescens. The Q10's of oxygen consumption and heart rate are quite different in O. flavescens but not as different in P. villosus. Although changes in the cardiovascular system, such as stroke volume, may also play a role in meeting increased oxygen demand, the features of the haemocyanin oxygen transport system, such as the absence of temperature sensitivity and a marked pH sensitivity, can also influence the maintenance of VO2 under temperature stress. The differences in the normal thermal habitats of the two species may be used to explain the distinctions between the evolved physiological responses to temperature increase shown by the two species.

Acclimatization↗
PubMed1994

Isolation and pharmacological characterization of four novel Na+ channel-blocking toxins from the scorpion Centruroides noxius Hoffmann.

Four novel Na+ channel-blocking toxins (numbered 6 to 9) were purified from the venom of the scorpion Centruroides noxius Hoffmann by gel filtration and high-performance liquid chromatography and their chemical and pharmacological properties were characterized. Amino acid analysis and SDS-PAGE of the pure toxins showed them to be composed of approximately 65 amino acid residues with a molecular mass of approximately 7,500 Da. The amino acid sequences of the newly isolated toxins displayed substantial similarity to those of previously isolated and characterized C. noxius toxins. Toxin 7, the most active toxin from this venom, selectively blocked the whole-cell inward Na+ current (INa) from guinea pig ventricular myocytes without altering the K+ or Ca2+ currents. Using rat brain synaptosomes, the specific binding parameters of 125I-Toxin 7 were determined: KD = 40 pM and Bmax = 1.8 pmol/mg protein. The binding was independent of membrane potential and was displaced by all Na+ channel-toxins from C. noxius venom, with K0.5s ranging from 60 pM to 60 nM. Tityus gamma-toxin, a toxin representative of beta-scorpion toxins, totally displaced 125I-Toxin 7 binding, but AaH II and Lqq V toxins, representative of alpha-scorpion toxins, had no effect. All four C. noxius toxins inhibited [3H]GABA uptake by synaptosomes with IC50 s similar to KD s. The toxin effect was not synergistic with veratridine. From these results, it was concluded that the newly purified toxins exert their effects by binding to Site 4 of the voltage-sensitive Na+ channel and must, therefore, be classified as beta-scorpion toxins.

Amino Acid Sequence↗
PubMed1996

Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels.

Maurotoxin is a toxin isolated from the venom of the Tunisian chactoid scorpion Scorpio maurus. It is a 34-amino-acid peptide cross-linked by four disulfide bridges. Maurotoxin competes with radiolabeled apamin and kaliotoxin for binding to rat-brain synaptosomes. Due to its very low concentration in venom (0.6% of the proteins), maurotoxin was chemically synthesized by means of an optimized solid-phase technique. The synthetic maurotoxin was characterized. It was lethal to mice following intracerebroventricular injection (LD50, 80 ng/mouse). The synthetic maurotoxin competed with 125I-apamin and 125I-kaliotoxin for binding to rat-brain synaptosomes with half-maximal effects at concentrations of 5 nM and 0.2 nM, respectively. Synthetic maurotoxin was tested on K+ channels and was found to block the Kv1.1, Kv1.2, and Kv1.3 currents with half-maximal blockage (IC50) at 37, 0.8 and 150 nM, respectively. Thus, maurotoxin is a scorpion toxin with four disulfide bridges that acts on K+ channels. The half-cystine pairings of synthetic maurotoxin were identified by enzymatic cleavage. The pairings were Cys3-Cys24, Cys9-Cys29, Cys13-Cys19 and Cys31-Cys34. This disulfide organization is unique among known scorpion toxins. The physicochemical and pharmacological properties of synthetic maurotoxin were indistinguishable from those of natural maurotoxin, which suggests that natural maurotoxin adopts the same half-cystine pairing pattern. The conformation of synthetic maurotoxin was investigated by means of circular dichroism spectroscopy and molecular modeling. In spite of its unusual half-cystine pairings, the synthetic-maurotoxin conformation appears to be similar to that of other short scorpion toxins.

Amino Acid Sequence↗
PubMed1997

1H-NMR-derived secondary structure and overall fold of a natural anatoxin from the scorpion Androctonus australis hector.

The venom of the scorpion Androctonus australis hector contains several protein neurotoxins of which structure and structure/activity relationships have been extensively studied. It also contains polypeptides such as Aah STR1, which are not toxic, while having highly similar sequences to fully active toxins. We have determined the solution structure of Aah STR1 by use of conventional two-dimensional NMR techniques followed by distance-geometry and energy minimization. We have demonstrated that, despite its lack of toxicity, Aah STR1 is structurally highly related to anti-mammal scorpion toxins specific for Na+ channels. The calculated structure is composed of a short alpha-helix (residues 26-33) connected by a tight turn to a three-stranded antiparallel beta-sheet (sequences 3-6, 38-41 and 44-48). This beta-sheet is right-handed twisted as usual for such secondary structures. The beta-turn connecting the strands 38-41 and 44-48 belongs to type II'. The overall fold of Aah STR1 is typical of beta-type scorpion toxins. This is, however, the first example of such a fold in Old World scorpion toxins. Either the absence of a basic residue in position 63 or the high mobility of loops, compared to active beta-type neurotoxins, may explain the lack of activity of this protein.

Amino Acid Sequence↗