1bmr
From Proteopedia
(New page: 200px<br /><applet load="1bmr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bmr" /> '''ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIUR...) |
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| - | [[Image:1bmr.jpg|left|200px]]<br /><applet load="1bmr" size=" | + | [[Image:1bmr.jpg|left|200px]]<br /><applet load="1bmr" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, 25 STRUCTURES'''<br /> | '''ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, 25 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | NMR structures of a new toxin from the scorpion Leiurus quinquestriatus | + | NMR structures of a new toxin from the scorpion Leiurus quinquestriatus hebraeus (Lqh III) have been investigated in conjunction with its pharmacological properties. This toxin is proposed to belong to a new group of scorpion toxins, the alpha-like toxins that target voltage-gated sodium channels with specific properties compared with the classical alpha-scorpion toxins. Electrophysiological analysis showed that Lqh III inhibits a sodium current inactivation in the cockroach axon, but induces in addition a resting depolarization due to a slowly decaying tail current atypical to other alpha-toxin action. Binding studies indicated that radiolabeled Lqh III binds with a high degree of affinity (Ki=2.2 nM) on cockroach sodium channels and that the alpha-toxin from L quinquestriatus hebraeus highly active on insects (LqhalphaIT) and alpha-like toxins compete at low concentration for its receptor binding site, suggesting that the alpha-like toxin receptor site is partially overlapping with the receptor site 3. Conversely, in rat brain, Lqh III competes for binding of the most potent anti-mammal alpha-toxin from Androctonus australis Hector venom (AaH II) only at very high concentration.The NMR structures were used for the scrutiny of the similarities and differences with representative scorpion alpha-toxins targeting the voltage-gated sodium channels of either mammals or insects. Three turn regions involved in the functional binding site of the anti-insect LqhalphaIT toxin reveal significant differences in the Lqh III structure. The electrostatic charge distribution in the Lqh III toxin is also surprisingly different when compared with the anti-mammal alpha-toxin AaH II. Similarities in the electrostatic charge distribution are, however, recognized between alpha-toxins highly active on insects and the alpha-like toxin Lqh III. This affords additional important elements to the definition of the new alpha-like group of scorpion toxins and the mammal versus insect scorpion toxin selectivities. |
==About this Structure== | ==About this Structure== | ||
| - | 1BMR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1BMR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BMR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gordon, D.]] | [[Category: Gordon, D.]] | ||
[[Category: Krimm, I.]] | [[Category: Krimm, I.]] | ||
| - | [[Category: Lancelin, J | + | [[Category: Lancelin, J M.]] |
[[Category: Pelhate, M.]] | [[Category: Pelhate, M.]] | ||
[[Category: Sautiere, P.]] | [[Category: Sautiere, P.]] | ||
| Line 25: | Line 25: | ||
[[Category: sodium channel inhibitor]] | [[Category: sodium channel inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:57:04 2008'' |
Revision as of 09:57, 21 February 2008
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ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, 25 STRUCTURES
Overview
NMR structures of a new toxin from the scorpion Leiurus quinquestriatus hebraeus (Lqh III) have been investigated in conjunction with its pharmacological properties. This toxin is proposed to belong to a new group of scorpion toxins, the alpha-like toxins that target voltage-gated sodium channels with specific properties compared with the classical alpha-scorpion toxins. Electrophysiological analysis showed that Lqh III inhibits a sodium current inactivation in the cockroach axon, but induces in addition a resting depolarization due to a slowly decaying tail current atypical to other alpha-toxin action. Binding studies indicated that radiolabeled Lqh III binds with a high degree of affinity (Ki=2.2 nM) on cockroach sodium channels and that the alpha-toxin from L quinquestriatus hebraeus highly active on insects (LqhalphaIT) and alpha-like toxins compete at low concentration for its receptor binding site, suggesting that the alpha-like toxin receptor site is partially overlapping with the receptor site 3. Conversely, in rat brain, Lqh III competes for binding of the most potent anti-mammal alpha-toxin from Androctonus australis Hector venom (AaH II) only at very high concentration.The NMR structures were used for the scrutiny of the similarities and differences with representative scorpion alpha-toxins targeting the voltage-gated sodium channels of either mammals or insects. Three turn regions involved in the functional binding site of the anti-insect LqhalphaIT toxin reveal significant differences in the Lqh III structure. The electrostatic charge distribution in the Lqh III toxin is also surprisingly different when compared with the anti-mammal alpha-toxin AaH II. Similarities in the electrostatic charge distribution are, however, recognized between alpha-toxins highly active on insects and the alpha-like toxin Lqh III. This affords additional important elements to the definition of the new alpha-like group of scorpion toxins and the mammal versus insect scorpion toxin selectivities.
About this Structure
1BMR is a Single protein structure of sequence from Leiurus quinquestriatus hebraeus with as ligand. Full crystallographic information is available from OCA.
Reference
NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus quinquestriatus hebraeus., Krimm I, Gilles N, Sautiere P, Stankiewicz M, Pelhate M, Gordon D, Lancelin JM, J Mol Biol. 1999 Jan 29;285(4):1749-63. PMID:9917409
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