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==NMR structural studies of a potassium channel / charybdotoxin complex== | |||
<StructureSection load='2a9h' size='340' side='right'caption='[[2a9h]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2a9h]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus] and [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A9H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=2a9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a9h OCA], [https://pdbe.org/2a9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a9h RCSB], [https://www.ebi.ac.uk/pdbsum/2a9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a9h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KCSA_STRLI KCSA_STRLI] Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).<ref>PMID:7489706</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a9/2a9h_consurf.spt"</scriptWhenChecked> | |||
<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=2a9h ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ion channels play critical roles in signaling processes and are attractive targets for treating various diseases. Here we describe an NMR-based strategy for structural analyses of potassium channel-ligand complexes using KcsA (residues 1-132, with six mutations to impart toxin binding and to mimic the eukaryotic hERG channel). Using this approach, we determined the solution structure of KcsA in complex with the high-affinity peptide antagonist charybdotoxin. The structural data reveal how charybdotoxin binds to the closed form of KcsA and makes specific contacts with the extracellular surface of the ion channel, resulting in pore blockage. This represents the first direct structural information about an ion channel complexed to a peptide antagonist and provides an experimental framework for understanding and interpreting earlier mutational analyses. The strategy presented here overcomes many of the limitations of conventional NMR approaches to helical membrane protein structure determination and can be applied in the study of the binding of druglike molecules to this important class of proteins. | |||
Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.,Yu L, Sun C, Song D, Shen J, Xu N, Gunasekera A, Hajduk PJ, Olejniczak ET Biochemistry. 2005 Dec 6;44(48):15834-41. PMID:16313186<ref>PMID:16313186</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2a9h" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
[[Category: | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Leiurus hebraeus]] | |||
[[Category: Streptomyces lividans]] | [[Category: Streptomyces lividans]] | ||
[[Category: Gunasekera | [[Category: Gunasekera A]] | ||
[[Category: Hajduk | [[Category: Hajduk PJ]] | ||
[[Category: Olejniczak | [[Category: Olejniczak ET]] | ||
[[Category: Shen | [[Category: Shen J]] | ||
[[Category: Song | [[Category: Song D]] | ||
[[Category: Sun | [[Category: Sun C]] | ||
[[Category: Xu | [[Category: Xu N]] | ||
[[Category: Yu | [[Category: Yu L]] | ||
Latest revision as of 03:46, 21 November 2024
NMR structural studies of a potassium channel / charybdotoxin complexNMR structural studies of a potassium channel / charybdotoxin complex
Structural highlights
FunctionKCSA_STRLI Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).[1] 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 PubMedIon channels play critical roles in signaling processes and are attractive targets for treating various diseases. Here we describe an NMR-based strategy for structural analyses of potassium channel-ligand complexes using KcsA (residues 1-132, with six mutations to impart toxin binding and to mimic the eukaryotic hERG channel). Using this approach, we determined the solution structure of KcsA in complex with the high-affinity peptide antagonist charybdotoxin. The structural data reveal how charybdotoxin binds to the closed form of KcsA and makes specific contacts with the extracellular surface of the ion channel, resulting in pore blockage. This represents the first direct structural information about an ion channel complexed to a peptide antagonist and provides an experimental framework for understanding and interpreting earlier mutational analyses. The strategy presented here overcomes many of the limitations of conventional NMR approaches to helical membrane protein structure determination and can be applied in the study of the binding of druglike molecules to this important class of proteins. Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.,Yu L, Sun C, Song D, Shen J, Xu N, Gunasekera A, Hajduk PJ, Olejniczak ET Biochemistry. 2005 Dec 6;44(48):15834-41. PMID:16313186[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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