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[[Image:1lgl.gif|left|200px]]
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{{STRUCTURE_1lgl|  PDB=1lgl  |  SCENE=  }}
'''Solution structure of HERG-specific scorpion toxin BeKm-1'''


==Solution structure of HERG-specific scorpion toxin BeKm-1==
<StructureSection load='1lgl' size='340' side='right'caption='[[1lgl]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lgl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesobuthus_eupeus Mesobuthus eupeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LGL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1lgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lgl OCA], [https://pdbe.org/1lgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lgl RCSB], [https://www.ebi.ac.uk/pdbsum/1lgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lgl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KGX21_MESEU KGX21_MESEU] Blocks human and/or rat Kv11.1/KCNH2/ERG1, Kv11.2/KCNH6/ERG2 and Kv11.3/KCNH7/ERG3 by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry. Inhibition data are the following: hERG1 (reversible, Kd=7.7 nM (PubMed:16497878), IC(50)=3.3 nM (PubMed:11136720), IC(50)=11.9 nM (PubMed:21205913)), rERG1 (reversible, Kd=19 nM) (PubMed:16497878), hERG2 (reversible, Kd=77 nM) (PubMed:16497878), rERG2 (irreversible, Kd=4.2 nM) (PubMed:16497878), hERG3 (reversible, Kd=11.5 nM) (PubMed:16497878) and rERG3 (reversible, Kd=747 nM) (PubMed:16497878) potassium channels. Has also a minimal effect on rat ELK1/KCNH4 potassium channels (9% inhibition at 100 nM (PubMed:15137031)). Both this toxin and CnErgTx1 (AC Q86QT3) share mechanism of action and have overlapping binding sites on ERG1 (PubMed:12719233). The potency of these two toxins is not affected by elevating potassium ion concentration from 2 to 98 mM (PubMed:12719233). In addition, at high toxin concentrations, block of ERG1 macroscopic currents by these two toxins is incomplete (88%) (PubMed:12719233). The blockade by this toxin is preferentially closed channel state-dependent, with a component of open, but not inactive state-dependent blockade (PubMed:12860380). This toxin produces a concentration-dependent prolongation of QTc in the isolated rabbit heart (16.3% at 100 nM) (PubMed:21205913).<ref>PMID:11136720</ref> <ref>PMID:12719233</ref> <ref>PMID:12860380</ref> <ref>PMID:16497878</ref> <ref>PMID:21205913</ref> <ref>PMID:8617371</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.


==Overview==
New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.,Korolkova YV, Bocharov EV, Angelo K, Maslennikov IV, Grinenko OV, Lipkin AV, Nosyreva ED, Pluzhnikov KA, Olesen SP, Arseniev AS, Grishin EV J Biol Chem. 2002 Nov 8;277(45):43104-9. Epub 2002 Jul 31. PMID:12151390<ref>PMID:12151390</ref>
The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1LGL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mesobuthus_eupeus Mesobuthus eupeus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LGL OCA].
</div>
<div class="pdbe-citations 1lgl" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1., Korolkova YV, Bocharov EV, Angelo K, Maslennikov IV, Grinenko OV, Lipkin AV, Nosyreva ED, Pluzhnikov KA, Olesen SP, Arseniev AS, Grishin EV, J Biol Chem. 2002 Nov 8;277(45):43104-9. Epub 2002 Jul 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12151390 12151390]
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mesobuthus eupeus]]
[[Category: Mesobuthus eupeus]]
[[Category: Single protein]]
[[Category: Angelo K]]
[[Category: Angelo, K.]]
[[Category: Arseniev AS]]
[[Category: Arseniev, A S.]]
[[Category: Bocharov EV]]
[[Category: Bocharov, E V.]]
[[Category: Grinenko OV]]
[[Category: Grinenko, O V.]]
[[Category: Grishin EV]]
[[Category: Grishin, E V.]]
[[Category: Korolokova YV]]
[[Category: Korolokova, Y V.]]
[[Category: Lipkin AV]]
[[Category: Lipkin, A V.]]
[[Category: Maslennikov IV]]
[[Category: Maslennikov, I V.]]
[[Category: Nosireva ED]]
[[Category: Nosireva, E D.]]
[[Category: Olesen S-P]]
[[Category: Olesen, S P.]]
[[Category: Pluzhnikov KA]]
[[Category: Pluzhnikov, K A.]]
[[Category: Alpha-beta motif]]
[[Category: Cysteine-knot motif]]
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