Anti‐Insect Toxin 5 (Aalts) from <i>Androctonus Australis</i>

Nakagawa, Yoshiaki; Lee, Young Moo; Lehmberg, Elisabeth; Herrmann, Robert O.; Moskowitz, Haim; Jones, A. Daniel; Hammock, Bruce D.

doi:10.1111/j.1432-1033.1997.t01-1-00496.x

Cited by 30 publications

(22 citation statements)

References 30 publications

(39 reference statements)

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“…(B) Sequences of eight Lqh-dprIT 3 variants deduced from the nucleotide sequences of the isolated cDNA clones, which were pulled out from the cDNA library by colony hybridization (28) using Lqh-dprIT 3 -cDNA(∆5′) as a probe. (C) Sequence comparison among a variety of scorpion depressant toxins: LqhIT 2 from L. quinquestriatus hebraeus(14), BotIT 4 and BotIT 5 from Buthus occitanus tunetanus(18), LqqIT 2 from Leiurus quinquestriatus quinquestriatus(19), Bj from Buthotus judaicus(26), and AaIT 5 from Androctonus australis hector(20).…”

mentioning

confidence: 99%

Genetic Polymorphism and Expression of a Highly Potent Scorpion Depressant Toxin Enable Refinement of the Effects on Insect Na Channels and Illuminate the Key Role of Asn-58

et al. 2005

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We isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus an extremely active anti-insect selective depressant toxin, Lqh-dprIT(3). Cloning of Lqh-dprIT(3) revealed a gene family encoding eight putative polypeptide variants (a-h) differing at three positions (37A/G, 50D/E, and 58N/D). All eight toxin variants were expressed in a functional form, and their toxicity to blowfly larvae, binding affinity for cockroach neuronal membranes, and CD spectra were compared. This analysis links Asn-58, which appears in variants a-d, to a toxin conformation associated with high binding affinity for insect sodium channels. Variants e-h, bearing Asp-58, exhibit a different conformation and are less potent. The importance of Asn-58, which is conserved in other depressant toxins, was further validated by construction and analysis of an N58D mutant of the well-characterized depressant toxin, LqhIT(2). Current and voltage clamp assays using the cockroach giant axon have shown that despite the vast difference in potency, the two types of Lqh-dprIT(3) variants (represented by Lqh-dprIT(3)-a and Lqh-dprIT(3)-e) are capable of blocking the action potentials (manifested as flaccid paralysis in blowfly larvae) and shift the voltage dependence of activation to more negative values, which typify the action of beta-toxins. Moreover, the stronger and faster shift in voltage dependence of activation and lack of tail currents observed in the presence of Lqh-dprIT(3)-a suggest an extremely efficient trapping of the voltage sensor compared to that of Lqh-dprIT(3)-e. The current clamp assays revealed that repetitive firing of the axon, which is reflected in contraction paralysis of blowfly larvae, can be obtained with either the less potent Lqh-dprIT(3)-e or the highly potent Lqh-dprIT(3)-a at more negative membrane potentials. Thus, the contraction symptoms in flies are likely to be dominated by the resting potential of neuronal membranes. This study clarifies the electrophysiological basis of the complex symptoms induced by scorpion depressant toxins in insects, and highlights for the first time molecular features involved in their activity.

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confidence: 99%

Genetic Polymorphism and Expression of a Highly Potent Scorpion Depressant Toxin Enable Refinement of the Effects on Insect Na Channels and Illuminate the Key Role of Asn-58

et al. 2005

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“…Few general features can be assigned to the different groups of toxins. The N-terminal is free and the C-terminal histidine is amidated (as Buthus and Leiurus), only one of these depressant anti-insect toxins has been described in Androctonus venom so far (Nakagawa et al 1997). The rare and most active α-type toxins described in New-World Buthidae (as Centruroides and Tityus) venoms have a β-loop of intermediate size, sharing this characteristic with Old-World depressant anti-insect toxins which, on the contrary, exhibit a β-type activity and a different pharmacological effect .…”

Section: Secondary and Tertiary Structuresmentioning

confidence: 99%

“…AaH IT5, from the Androctonus australis hector venom, is very potent against the tobacco budworm, Heliothis virescens, and shows distinct insect specificity (Nakagawa et al 1997). However, some molecules giving a weak progressive onset of flaccid paralysis in insects were found.…”

Section: Anti-insect Depressant B-toxinsmentioning

confidence: 99%

Scorpion Venoms

2015

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In recent years, the field of toxinology has expanded substantially. On the one hand it studies venomous animals, plants and micro organisms in detail to understand their mode of action on targets. While on the other, it explores the biochemical composition, genomics and proteomics of toxins and venoms to understand their three interaction with life forms (especially humans), development of antidotes and exploring their pharmacological potential. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy and pharmacology. In addition, there is a fast-developing applied subfield, clinical toxinology, which deals with understanding and managing medical effects of toxins on human body. Given the huge impact of toxin-based deaths globally, and the potential of venom in generation of drugs for so-far incurable diseases (for example, diabetes, chronic pain), the continued research and growth of the field is imminent. This has led to the growth of research in the area and the consequent scholarly output by way of publications in journals and books. Despite this ever-growing body of literature within biomedical sciences, there is still no all-inclusive reference work available that collects all of the important biochemical, biomedical and clinical insights relating to toxinology. Composed of 11 volumes, Toxinology provides comprehensive and authoritative coverage of the main areas in toxinology, from fundamental concepts to new developments and applications in the field. Each volume comprises a focused and carefully chosen collection of contributions from leading names in the subject.

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“…Several insect-selective toxins have been identified and purified from scorpions collected in different geographical locations [2,11,15-18]. However, the Indian red scorpion, Mesobuthus tamulus, known for its severe toxicity [19,20] received little attention in this regard.…”

Section: Introductionmentioning

confidence: 99%