Delta-Palutoxin: Difference between revisions
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'''Delta-Palutoxins''' (δ-Palutoxins) is the generic name for a homologous group of four insect specific [[toxins]] extracted from the venom of the spider Paracoelotes luctuosus, with a high [[toxicity]] against the [[Spodoptera litura]] larve by inhibiting [[sodium channel]] inactivation, leading to strong paralytic activity and eventually to the dead of the insect.<ref name="one">Corzo G, Escoubas P, et al.(2000). “Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae)” Eur. J. Biochem. 267, 5783-5795.</ref> |
'''Delta-Palutoxins''' (δ-Palutoxins) is the generic name for a homologous group of four insect specific [[toxins]] extracted from the venom of the spider Paracoelotes luctuosus, with a high [[toxicity]] against the [[Spodoptera litura]] larve by inhibiting [[sodium channel]] inactivation, leading to strong paralytic activity and eventually to the dead of the insect.<ref name="one">Corzo G, Escoubas P, et al.(2000). “Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae)” Eur. J. Biochem. 267, 5783-5795. PMID 10971590</ref> |
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==Source== |
==Source== |
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Revision as of 11:32, 17 October 2012
 | This article possibly contains original research. (October 2012) |
Delta-Palutoxins (δ-Palutoxins) is the generic name for a homologous group of four insect specific toxins extracted from the venom of the spider Paracoelotes luctuosus, with a high toxicity against the Spodoptera litura larve by inhibiting sodium channel inactivation, leading to strong paralytic activity and eventually to the dead of the insect.[1]
Source
δ-Palutoxins are extracted from the venom of the spider Paracoelotes luctuosus.[1] This venom has the highest toxicity against the Spodoptera litura larve, which is a known cause of the crop pest in agriculture.
Chemistry
There are four toxic sub fractions known in the venom against the Spodoptera litura larve namely δ-Palutoxin IT1, d-Palutxoin IT2 d -Palutoxin IT3 and δ-Palutoxin IT4.[1] These toxins are 36-37 amino acids long and very homologous to each other.[1] The concentrations of the different subtypes in the venom, molecular masses and acidity level of the subtypes are listed below.
| Toxin Subtype | Concentration in
venom (nmole/10µL) |
Molecular mass (kDa) | Acidity level |
|---|---|---|---|
| δ-Palutoxin IT1 | 1,0 | 4,03 | Neutral |
| δ-Palutoxin IT2 | 2,6 | 4,12 | Slightly basic |
| δ-Palutoxin IT3 | 1,3 | 3,93 | Acidic |
| δ-Palutoxin IT4 | 1,9 | 4,05 | Slightly basic |
δ-Palutoxins are very compact proteins due to their four disulfide bridges.[2] These bindings result in a disulfide pseudo-knot, characteristic for a class of toxins that contain the ‘inhibitor cysteine-knot motif’ (ICK). This cysteine knot is responsible for their high in vivo stability.[2] Members of the ICK family are characterized by a triple-stranded, antiparallel ß-sheet structure, stabilized by disulfide bridges. Within this fold-class, the biological activities of the toxins are very diverse. The disulfide bonding pattern found in δ-Palutoxins is very similar to the pattern seen in µ-Agatoxins.[1] This indicates strong homologies with the µ-Agatoxins from Agelenopsis aperta.[3]
Target
Voltage-gated sodium channels have neurotoxin binding sites on their a-subunit[4] which are called neurotoxin receptor sites 1-7. δ-Palutoxins bind to receptor site 4 of insect voltage-gated sodium channels.[4] Receptor site 4 neurotoxins bind to the S1-S2 and S3-S4 extracellular loops in domain II of the a-subunit of the channel.[2]
Mode of action
δ-Palutoxin-IT1 and δ-Palutoxin-IT2 affect voltage-gated sodium channels by causing faster configuration from the inactive state to the closed state.[5] The time-to-peak current and the time constant of inactivation of the voltage-gated sodium channels are not affected by the toxin which indicates that the configuration from the closed to open state and from the open to inactivated state is normal.[5] The skipping of the inactivation phase results in sodium current flow at membrane potentials which under normal conditions channels are closed.[1] This excessive sodium influx leads to a high concentration of calcium in the muscles, which causes slow paralysis. This slow paralysis is characterized by muscle spasm and loss of water through the body wall. Eventually, the insects will die because they dry out.[4] The effect of δ-Palutoxins on voltage-gated sodium channels is similar as seen in a-like scorpion toxins.[6][7]
Toxicity
The four δ-Palutoxins show a strong paralytic activity against the Spodoptera litura larve but also against some other insects. The LD50 values for δ-Palutoxin-IT1 to IT3 are ranged from 9,5 – 24,7 µg per gram insect.[1] δ-Palutoxin-IT1 is the most active toxin followed by δ-Palutoxin-IT2, and δ-Palutoxin-IT4 has the lowest activity. δ-Palutoxins are insect selective.[1] Their possible effect on mammals was tested in mice but here it didn’t show a persistent toxic effect.[1] The structural basis for the selectivity of these toxins for insects over the mammalian sodium ion channels is still largely unknown.[3]
Therapeutic use
Spider venoms have been showed the most lethal venoms against pest insects.[8] Knowledge about specific spider toxins such as δ-Palutoxins might contribute to the production of selective, fast-acting pathogens such as recombinant viruses expressing toxins, also named baculoviruses.[1] These baculoviruses might be used as effective, safer insecticides in the agriculture against pest insects such as the Spodoptera litura larve.
References
- ^ a b c d e f g h i j Corzo G, Escoubas P, et al.(2000). “Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae)” Eur. J. Biochem. 267, 5783-5795. PMID 10971590 Cite error: The named reference "one" was defined multiple times with different content (see the help page).
- ^ a b c Nicholson G, (2007), “Insect-selective spider toxins targeting voltage-gated sodium channels” Toxicon, 49, 490-512. PMID 17223149 Cite error: The named reference "two" was defined multiple times with different content (see the help page).
- ^ a b Billen B, Vassilevski A, et al. (2010), “Unique Bell-shaped Voltage-dependent modulation of Na+ channel gating by novel insect-selective toxins from the spider Agelena orientalis”Journal of biological chemistry, 285(24), 18545-18554. PMID 20385552 Cite error: The named reference "three" was defined multiple times with different content (see the help page).
- ^ a b c Corzo, Escoubas P. et.al (2005) “A spider toxin that induces a typical effect of scorpion α-toxins but competes with β-toxins on binding to insect sodium channels” Biochemistry, 44, 1542-1549. PMID 15683238 Cite error: The named reference "four" was defined multiple times with different content (see the help page).
- ^ a b Ferrat G, et.al (2005) “Solution structure of two insect specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel” Journal of proteins: structure, proteins and bioinformatics 59, 368-379.
- ^ Gurevitz, M., et al. (1998) “Sodium channel modifiers from scorpion venom: structure-activity relationship, mode of action and application”, Toxicon 36, 1671 – 1682.
- ^ Cestele, S., et al. (1999) “Scorpion alpha-like toxins, toxic to both mammals and insects, differentially interact with receptor site 3 on voltage-gated sodium channels in mammals and insects”, Eur. J. Neurosci. 11, 975 – 985.
- ^ Quistad, G.B., Dennis, P.A. & Skinner,W.S. (1992) “Insecticidal activity of spider (Araneae), centipede (Chilopoda), scorpion (Scorpionida), and snake (Serpentes) venoms”, J. Econ. Entomol. 85, 33-39.