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Iberiotoxin

From Wikipedia, the free encyclopedia
The amino acid sequence of Iberiotoxin[1]
Pyr - Phe - Thr - Asp - Val - Asp - Cys - Ser - Val - Ser - Lys - Glu - Cys - Trp - Ser - Val - Cys - Lys - Asp - Leu - Phe - Gly - Val - Asp - Arg - Gly - Lys - Cys - Met - Gly - Lys - Lys - Cys - Arg - Cys - Tyr - Gln - OH
Disulfide bridges: Cys7 - Cys28, Cys13 - Cys33, Cys17 - Cys35

Iberiotoxin (IbTX) is anion channeltoxin purified from the Eastern Indian redscorpionHottentotta tamulus.Iberiotoxin selectively inhibits thecurrent through large-conductancecalcium-activated potassium channels.

Chemistry

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Iberiotoxin is a 37-amino acidpeptide. The formula is C179H274N50O55S7.[2] It is also known as "Potassium channel toxin alpha-KTx 1.3" or IbTx. The completeamino acid sequence has been defined and it displays 68%sequence homology withcharybdotoxin.[1]

Target and mode of action

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Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK orBK channels) with high affinity (Kd ~1 nM).[3] It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.[3]

Toxicity

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The venom produces mainly cardiopulmonary abnormalities like circulatory derangements,myocarditis and changes in cardiacsarcolemmalATPase and by these abnormalities it can finally cause death. In ruralIndia the scorpion and its venom is a commonly known factor of children's death. The venom initially causes transientcholinergic stimulation (vomiting, profusesweating,bradycardia,priapism,hypersalivation, andhypotension) which is followed by sustainedadrenergic hyperactivity (hypertension,tachycardia, and myocardial failure). The adrenergic phase but not the cholinergic phase is a dose-dependent phenomenon.[4]

Treatment

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Treatment is mainly symptomatic. Localpain is treated by injectingdehydroemetine at the site of the sting.Hypovolaemia is corrected by oral rehydration solution. Agitated, confused and non-cooperative patients are given a 5%dextrosesaline drip. Patients withhypertension on admission are given a single dose of 5 mgsublingualnifedipine and oralprazosin. The blood pressure in patients with hypertension is controlled with sublingual nifedipine alone. Patients with pulmonaryoedema are propped up and given intravenousaminophylline,intravenous sodium bicarbonate, oralprazosin, andoxygen by mask.[4]

References

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  1. ^abGalvez, A; Gimenez-Gallego, G; Reuben, JP; Roy-Contancin, L; Feigenbaum, P; Kaczorowski, GJ; Garcia, ML (1990)."Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Hottentotta tamulus".The Journal of Biological Chemistry.265 (19):11083–90.doi:10.1016/S0021-9258(19)38560-6.hdl:10261/177752.PMID 1694175.
  2. ^Ferrat, G; Bernard, C; Fremont, V; Mullmann, TJ; Giangiacomo, KM; Darbon, H (2001). "Structural basis for alpha-K toxin specificity for K+ channels revealed through the solution 1H NMR structures of two noxiustoxin-iberiotoxin chimeras".Biochemistry.40 (37):10998–1006.doi:10.1021/bi010228e.PMID 11551195.
  3. ^abCandia, S; Garcia, ML; Latorre, R (1992)."Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel".Biophysical Journal.63 (2):583–90.Bibcode:1992BpJ....63..583C.doi:10.1016/S0006-3495(92)81630-2.PMC 1262182.PMID 1384740.
  4. ^abBawaskar, HS; Bawaskar, PH (1992)."Management of the cardiovascular manifestations of poisoning by the Indian red scorpion (Hottentotta tamulus)".British Heart Journal.68 (5):478–80.doi:10.1136/hrt.68.11.478.PMC 1025191.PMID 1467032.
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