1px9
From Proteopedia
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==Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel== | ==Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel== | ||
| - | <StructureSection load='1px9' size='340' side='right' caption='[[1px9 | + | <StructureSection load='1px9' size='340' side='right'caption='[[1px9]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1px9]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1px9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PX9 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1px9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1px9 OCA], [https://pdbe.org/1px9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1px9 RCSB], [https://www.ebi.ac.uk/pdbsum/1px9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1px9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/KGX11_CENNO KGX11_CENNO] Blocks human and rat Kv11.1/KCNH2/ERG1 and Kv11.3/KCNH7/ERG3, as well as rat (but not human) Kv11.2/KCNH6/ERG2 (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425) by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry (PubMed:11755529, PubMed:11864985, PubMed:17369411, PubMed:20600425). Inhibition data are the following: hERG1 (reversible, IC(50)~7 nM) (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425), rERG1 (reversible, Kd=6.8 nM) (PubMed:16497878), rERG2 (irreversible, Kd=2.8 nM) (PubMed:16497878), hERG3 (irreversible, Kd=4.05 nM) (PubMed:16497878) and rERG3 (reversible, Kd=38.1 nM) (PubMed:16497878) potassium channels. The toxin potency is not affected by elevating potassium ion concentration from 2 to 98 mM (PubMed:11864985). This toxin only blocks channels in a closed state (PubMed:12860380). At high toxin concentrations, block of Kv11.1/KCNH2/ERG1 macroscopic current is incomplete (93.5%). This suggests a kinetic mechanism model with two different states of toxin-channel binding (T+C=TC*=TC; in the TC* state, the toxin binds the channel but does not occlude the pore, whereas in the TC state the toxin binds and occludes the pore). In this model, incomplete block is explained by the relatively fast dissociation rate from the blocked channel conformation (TC) relative to the rate of conversion of the toxin-channel encounter complex (TC*) to the blocked channel conformation (TC) (PubMed:17369411).<ref>PMID:10224238</ref> <ref>PMID:11755529</ref> <ref>PMID:11864985</ref> <ref>PMID:12860380</ref> <ref>PMID:16497878</ref> <ref>PMID:17369411</ref> <ref>PMID:20600425</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/px/1px9_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/px/1px9_consurf.spt"</scriptWhenChecked> | ||
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1px9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1px9" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Centruroides noxius]] | [[Category: Centruroides noxius]] | ||
| - | [[Category: Delepierre | + | [[Category: Large Structures]] |
| - | [[Category: Frenal | + | [[Category: Delepierre M]] |
| - | [[Category: Gurrola | + | [[Category: Frenal K]] |
| - | [[Category: Possani | + | [[Category: Gurrola GB]] |
| - | [[Category: Wecker | + | [[Category: Possani LD]] |
| - | [[Category: Wolff | + | [[Category: Wecker K]] |
| - | + | [[Category: Wolff N]] | |
| - | + | ||
Current revision
Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel
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