1bmr

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Current revision

ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, 25 STRUCTURES

Structural highlights

1bmr is a 1 chain structure with sequence from Leiurus hebraeus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 25 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SCL3_LEIHE Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. The dissociation is voltage-dependent. This alpha-like toxin is highly toxic to insects and competes with LqhaIT on binding to insect sodium channels. Differs from classical anti-mammalian alpha-toxins as it inhibits sodium channel inactivation in cell bodies of hippocampus brain neurons, on which the anti-mammalian Lqh2 is inactive, and is unable to affect Nav1.2 in the rat brain, on which Lqh2 is highly active. Moreover, its pharmacological properties are unique in that its binding affinity for insect channels drops >30-fold at pH 8.5 versus pH 6.5, and its rate of association with receptor site-3 on both insect and mammalian sodium channels is 4-15-fold slower compared with LqhaIT and Lqh2.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gilles N, Blanchet C, Shichor I, Zaninetti M, Lotan I, Bertrand D, Gordon D. A scorpion alpha-like toxin that is active on insects and mammals reveals an unexpected specificity and distribution of sodium channel subtypes in rat brain neurons. J Neurosci. 1999 Oct 15;19(20):8730-9. PMID:10516292
↑ Chen H, Gordon D, Heinemann SH. Modulation of cloned skeletal muscle sodium channels by the scorpion toxins Lqh II, Lqh III, and Lqh alphaIT. Pflugers Arch. 2000 Feb;439(4):423-32. PMID:10678738
↑ Chen H, Heinemann SH. Interaction of scorpion alpha-toxins with cardiac sodium channels: binding properties and enhancement of slow inactivation. J Gen Physiol. 2001 Jun;117(6):505-18. PMID:11382802
↑ Karbat I, Kahn R, Cohen L, Ilan N, Gilles N, Corzo G, Froy O, Gur M, Albrecht G, Heinemann SH, Gordon D, Gurevitz M. The unique pharmacology of the scorpion alpha-like toxin Lqh3 is associated with its flexible C-tail. FEBS J. 2007 Apr;274(8):1918-31. Epub 2007 Mar 9. PMID:17355257 doi:http://dx.doi.org/EJB5737
↑ Sautiere P, Cestele S, Kopeyan C, Martinage A, Drobecq H, Doljansky Y, Gordon D. New toxins acting on sodium channels from the scorpion Leiurus quinquestriatus hebraeus suggest a clue to mammalian vs insect selectivity. Toxicon. 1998 Aug;36(8):1141-54. PMID:9690781
↑ Krimm I, Gilles N, Sautiere P, Stankiewicz M, Pelhate M, Gordon D, Lancelin JM. NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus quinquestriatus hebraeus. J Mol Biol. 1999 Jan 29;285(4):1749-63. PMID:9917409 doi:10.1006/jmbi.1998.2418

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bmr"

@@ Line 3: / Line 3: @@
 <StructureSection load='1bmr' size='340' side='right'caption='[[1bmr]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bmr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BMR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bmr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BMR FirstGlance]. <br>
-</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</td></tr>
 <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bmr OCA], [https://pdbe.org/1bmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bmr RCSB], [https://www.ebi.ac.uk/pdbsum/1bmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bmr ProSAT]</span></td></tr>
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/1bmr_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
 </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bmr ConSurf].
 <div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
+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<ref>PMID:9917409</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1bmr" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 25: / Line 34: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Leiurus quinquestriatus hebraeus]]
+[[Category: Leiurus hebraeus]]
 [[Category: Gilles N]]
 [[Category: Gordon D]]

1bmr

From Proteopedia

Current revision

ALPHA-LIKE TOXIN LQH III FROM SCORPION LEIURUS QUINQUESTRIATUS HEBRAEUS, NMR, 25 STRUCTURES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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