Imperatoxin

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Imperatoxin I (IpTx) is a peptide toxin derived from the venom of the African scorpion Pandinus imperator .

Contents

There are two subtypes of this toxin:

Imperatoxin A

The toxin comes from the venom of the African scorpion Pandinus imperator . [1] The structure of IpTxa consists of:

The molecular weight of the toxin is 3.7 kDa.

IpTxa acts on the Ryanodine receptors (RyR), which are intracellular Ca2+ release channels mainly known for their role in regulating Ca2+ release from the sarcoplasmatic reticulum of striated muscles. [2] The peptide acts better on RyR type 1 than on type 3. RyR type 2 seems to be insensitive to IpTxa. [3]

The part of the peptide that looks like the II-III loop of the (DHPR) binds directly to RyR and enhances ryanodine binding to trigger Ca2+ release. [3]

Imperatoxin I

The toxin comes from the venom of the African scorpion Pandinus imperator . [1] The structure of IpTxi consists of:

The molecular weight of the toxin is 15 kDa.

Like IpTxa, IpTxi acts on RyR.

When an action potential reaches the muscle, RyR channels open and Ca2+ becomes available in the cell to induce contraction. The presence of Ca2+ induces the large subunit of IpTxi to hydrolyze the Sn2 fatty acyl bond from the membrane of the sarcoplasmatic reticulum. This process is executed by PLA2 activity. The freed fatty acids bind to the RyR itself or to a closely associated protein linked to gating. Binding of the RyR induces blocking of the channel. When the concentration of free fatty acids is low there will be an incomplete block of RyR; higher concentrations will give a complete block. [4]

Because IpTxi also works on the RyR channels of the heart muscles, it could potentially be used as a drug against arrhythmia. This has not yet been proven, and must be studied in vivo first. [5]

Related Research Articles

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The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released into the cell when necessary and then removed from the cell.

<span class="mw-page-title-main">Charybdotoxin</span> Chemical compound, scorpion neurotoxin

Charybdotoxin (ChTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker) that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. It is named after Charybdis, a sea monster from Greek myth.

<span class="mw-page-title-main">Emperor scorpion</span> Species of scorpion

The emperor scorpion(Pandinus imperator) is a species of scorpion native to rainforests and savannas in West Africa. It is one of the largest scorpions in the world and lives for six to eight years. Its body is black, but like other scorpions it glows pastel green or blue under ultraviolet light. It is a popular species in the pet trade, and is protected by CITES to prevent over-collecting that might affect the species' survival.

Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.

<span class="mw-page-title-main">Scyllatoxin</span> Scorpion toxin

Scyllatoxin (also leiurotoxin I) is a toxin, from the scorpion Leiurus quinquestriatus hebraeus, which blocks small-conductance Ca2+-activated K+ channels. It is named after Scylla, a sea monster from Greek mythology. Charybdotoxin is also found in the venom from the same species of scorpion, and is named after the sea monster Charybdis. In Greek mythology, Scylla and Charybdis lived on rocks on opposing sides of a narrow strait of water.

Ca<sub>v</sub>1.1 Mammalian protein found in humans

Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and the dihydropyridine receptor.

<span class="mw-page-title-main">Maurocalcine</span> Protein

Maurocalcine (MCa) is a protein, 33 Amino acid residues in length, isolated from the venom of the scorpion Maurus palmatus, which belongs to the family Chactidae, first characterized in 2000. The toxin is present in such small amounts that it could not be isolated to analyze it, so a chemical synthesis of this toxin was performed by the solid-phase technique so it could be fully characterized. It shares 82% sequence identity with imperatoxin A (IpTx A), a scorpion toxin from the venom of Pandinus imperator. IpTx A acts by modifying the activity of the type 1 ryanodine receptor of skeletal muscle. RyR controls the intracellular Ca2+ permeability of various cell types and is central in the process of excitation–contraction of muscle tissues. The synthesized toxin, sMCa is active on RyR1 and it binds onto a site different from that of ryanodine itself.

Helothermine is a toxin from the venom of the Mexican beaded lizard Heloderma horridum horridum. Helothermine inhibits ryanodine receptors, calcium channels and potassium channels. Helothermine can cause lethargy, partial paralysis of rear limbs and lowering of the body temperature.

<span class="mw-page-title-main">Pandinotoxin</span> Chemical compound

Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium channels

<span class="mw-page-title-main">Pandinus imperator (Pi3) toxin</span>

Pi3 toxin is a purified peptide derivative of the Pandinus imperator scorpion venom. It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, Pi2.

<span class="mw-page-title-main">Hadrucalcin</span> Peptide toxin from the venom of the scorpion Hadrurus gertschi

Hadrucalcin is a peptide toxin from the venom of the scorpion Hadrurus gertschi. Hadrucalcin modifies the Ryanodine receptor channels RyR1 and RyR2, found in the sarcoplasmic reticulum, to a long-lasting subconductance state, thus inducing the release of calcium from the sarcoplasmic reticulum.

HsTx1 is a toxin from the venom of the scorpion Heterometrus spinifer. HsTx1 is a very potent inhibitor of the rat Kv1.3 voltage-gated potassium channel.

Pi4 is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels.

LmαTX3 is an α-scorpion toxin from Lychas mucronatus. that inhibits fast inactivation of voltage gated sodium-channels (VGSCs).

Pi5 toxin is a peptide found in the venom of the African emperor scorpion Pandinus imperator. Pi5 inhibits human Kv1.2 and Kv1.3 channels as well as Drosophila Shaker B potassium channels.

<span class="mw-page-title-main">Wasabi receptor toxin</span>

Wasabi receptor toxin (WaTx) is the active component of the venom of the Australian black rock scorpion Urodacus manicatus. WaTx targets TRPA1, also known as the wasabi receptor or irritant receptor. WaTx is a cell-penetrating toxin that stabilizes the TRPA1 channel open state while reducing its Ca2+-permeability, thereby eliciting pain and pain hypersensitivity without the neurogenic inflammation that typically occurs in other animal toxins.

<span class="mw-page-title-main">Vejocalcin</span> Toxin

Vejocalcin is a toxin from the venom of the Mexican scorpion Vaejovis mexicanus. Vejocalcin is a member of the calcin family of toxins. It acts as a cell-penetrating peptide (CPP); it binds with high affinity and specificity to skeletal ryanodine receptor 1 (RYR1) of the sarcoplasmic reticulum, thereby triggering calcium release from intracellular Ca2+
 stores.

Intrepicalcin (ViCaTx1) is a short peptide toxin found in the venom of scorpion Vaejovis intrepidus. It is one of a group of short, basic peptides called calcins, which bind to ryanodine receptors (RyRs) and thereby trigger calcium release from the sarcoplasmic reticulum.

Crotoxin (CTX) is the main toxic compound in the snake venom of the South American rattlesnake, Crotalus durissus terrificus. Crotoxin is a heterodimeric beta-neurotoxin, composed of an acidic, non-toxic and non-enzymatic subunit (CA), and a basic, weakly toxic, phospholipase A2 protein (CB). This neurotoxin causes paralysis by both pre- and postsynaptic blocking of acetylcholine signalling.

References

  1. 1 2 Valdivia, Hector H.; Kirby, Mark S.; Lederer, W. Jonathan; Coronado, Roberto (1992). "Scorpion Toxins Targeted Against the Sarcoplasmic Reticulum Ca2+- Release Channel of Skeletal and Cardiac Muscle". Proceedings of the National Academy of Sciences. 89 (24): 12185–9. Bibcode:1992PNAS...8912185V. doi: 10.1073/pnas.89.24.12185 . JSTOR   2360882. PMC   50723 . PMID   1334561.
  2. ↑ Franzini-Armstrong, C; Protasi, F (1997). "Ryanodine receptors of striated muscles: A complex channel capable of multiple interactions". Physiological Reviews. 77 (3): 699–729. doi:10.1152/physrev.1997.77.3.699. PMID   9234963.
  3. 1 2 Simeoni, Ilenia; Rossi, Daniela; Zhu, Xinsheng; Garcı́a, Jesus; Valdivia, Hector H.; Sorrentino, Vincenzo (2001). "Imperatoxin A (IpTxa) from Pandinus imperator stimulates [3H]ryanodine binding to RyR3 channels". FEBS Letters. 508 (1): 5–10. Bibcode:2001FEBSL.508....5S. doi:10.1016/S0014-5793(01)03013-7. PMID   11707258. S2CID   24194429.
  4. ↑ Zamudio, F. Z.; Conde, R; Arévalo, C; Becerril, B; Martin, BM; Valdivia, HH; Possani, LD (1997). "The Mechanism of Inhibition of Ryanodine Receptor Channels by Imperatoxin I, a Heterodimeric Protein from the Scorpion Pandinus imperator". Journal of Biological Chemistry. 272 (18): 11886–94. doi: 10.1074/jbc.272.18.11886 . PMID   9115249.
  5. ↑ Santonastasi, Marco; Wehrens, Xander H T (2007). "Ryanodine receptors as pharmacological targets for heart disease". Acta Pharmacologica Sinica. 28 (7): 937–44. doi: 10.1111/j.1745-7254.2007.00582.x . PMID   17588328.
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