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| - | <StructureSection load='1lqh' size="400" color="" spin="on" Scene= caption='Scorpion toxin, [[1lqh]]' >
| + | #REDIRECT [[Potassium_channel_toxin]] |
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| - | ==Overview==
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| - | Scorpion toxins are 61- to 76-residue long proteins that modulate the gating properties of voltage-gated sodium channels. According to their mode of action and binding properties,scorpion toxins are divided into two major classes, alpha- and beta- toxins.
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| - | LqhαIT is a 64-residue scorpion α-toxin from [http://en.wikipedia.org/wiki/Deathstalker_scorpion Leiurus quinquestriatus hebraeus] (yellow scorpion) venom. Scorpion α-toxins prolong the action potential by inhibiting channel inactivation. The binding site of scorpion α-neurotoxins on voltage-gated sodium channels is named neurotoxin receptor site-3.
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| - | Scorpion α-toxins are similar in structure and exhibit a similar mode of action, but are very diverse in sequence and selectivity. Some scorpion α-neurotoxins show specificity for insect sodium channels and others are specific for mammalian sodium channels and exhibit different affinities to sodium channel subtypes in mammalian neurons. LqhαIT is the most insecticidal among scorpion α-toxins.
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| - | ==About this Structure==
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| - | The structure of LqhαIT was solved by NMR (1) and was found to resemble that of other scorpion toxins: a core composed of an <scene name='1lqh/Helix/2'>α-helix</scene> packed against a three stranded anti-parallel <scene name='1lqh/Sheet/1'>β-sheet</scene> and stabilized by four disulfide bonds.
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| - | ==The Binding-Site==
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| - | Mutational studies identified residues <scene name='1lqh/Mutations/2'>Lys8, Tyr10, Phe17, Arg18, Trp38, Asn44 and the C- tail region (Ile57, Arg58, Val59, Lys62 and Arg64)</scene> of LqhαIT as important for the interaction with sodium channels (2).
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| - | NMR studies of LqhαIT with a peptide derived from part of neurotoxin receptor site-3 (D4S3-S4) identified residues <scene name='1lqh/Nmr/1'>Lys8, Asn9, Cys12, Val13, Arg18, Trp38, Ala39 and Arg58</scene> of LqhαIT as participating in binding to that extra-cellular part of the sodium channel (3).
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| - | Both methods led to the identification of two regions on the surface of LqhαIT that participate in binding of the toxin to neurotoxin receptor site-3 on sodium channels.
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| - | </StructureSection>
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| - | ==3D structures of scorpion toxin==
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| - | [[1pnh]] – AmST P05-NH2 – ''Androctonus mauretanicus'' – NMR<BR />
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| - | [[1acw]] - AmST P01 – NMR<BR />
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| - | [[2sn3]] – ST – ''Centruroides exilicauda''<BR />
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| - | [[1ptx]] – ST – ''Androctonus australis''<BR />
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| - | [[1sco]] – ST OSK1 – ''Orthochirus scrobiculosus'' – NMR<BR />
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| - | [[1lqh]], [[1lqi]] – ST α – ''Leiurus quinquestriatus hebraeus'' – NMR<BR />
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| - | [[1snb]] – MmST BMK M8 – ''Mesobuthus martensii''<BR />
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| - | [[1sn1]] - MmST BMK M1<BR />
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| - | [[1pvz]] - MmST BMP07 – NMR<BR />
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| - | [[2k9o]] – ST VM24 – synthetic - NMR<BR />
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| - | ==References==
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| - | (1) Tugarinov, V., Kustanovich, I., Zilberberg, N., Gurevitz, M. Anglister, J. Solution structures of a highly insecticidal recombinant scorpion alpha-toxin and a mutant with increased activity. Biochemistry 36, 2414-24 (1997).
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| - | [http://www.ncbi.nlm.nih.gov/pubmed/9054546?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum PMID: 9054546]
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| - | (2) Karbat, I., Frolow, F., Froy, O., Gilles, N., Cohen, L., Turkov, M., Gordon, D. Gurevitz, M. Molecular basis of the high insecticidal potency of scorpion alpha-toxins. J. Biol. Chem. 279, 31679-86 (2004).
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| - | [http://www.ncbi.nlm.nih.gov/pubmed/15133045?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum PMID: 15133045]
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| - | (3) Schnur, E., Turkov, M., Kahn, R., Gordon, D., Gurevitz, M., Anglister, J. NMR Analysis of interaction of Lqh(alpha)IT scorpion toxin with a peptide corresponding to the D4/S3-S4 loop of insect para voltage-gated sodium channel. Biochemistry 47(3), 911-21 (2008).
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| - | [http://www.ncbi.nlm.nih.gov/pubmed/18154318?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum PMID: 18154318]
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| - | Created with the participation of [[User:Eran Hodis|Eran Hodis]], [[User:Einat Schnur|Einat Schnur]], [[User:Jaime Prilusky|Jaime Prilusky]]
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| - | [[Category:Topic Page]]
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