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1agt
From Proteopedia
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| - | [[Image:1agt.gif|left|200px]] | ||
| - | + | ==SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY== | |
| - | + | <StructureSection load='1agt' size='340' side='right'caption='[[1agt]]' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[1agt]] 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=1AGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AGT FirstGlance]. <br> | |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 17 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=1agt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1agt OCA], [https://pdbe.org/1agt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1agt RCSB], [https://www.ebi.ac.uk/pdbsum/1agt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1agt ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | | | + | == Function == |
| - | + | [https://www.uniprot.org/uniprot/KAX32_LEIHE KAX32_LEIHE] Potent inhibitor of the Shaker potassium channels and its mammalian homologs (Kv1.1/KCNA1, Kv1.3/KCNA3, Kv1.6/KCNA6) (Ki<1 nM for all channels) (PubMed:20007782, PubMed:8204618). Also blocks Kv1.2/KCNA2 (IC(50)=26.8 nM) (PubMed:20007782, PubMed:8204618). It also shows a weak interaction with nicotinic acetylcholine receptors (nAChR), suggesting it may weakly inhibit it (PubMed:31276191).<ref>PMID:20007782</ref> <ref>PMID:8204618</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/ag/1agt_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=1agt ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta-sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions. | The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta-sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions. | ||
| - | + | Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry.,Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G Protein Sci. 1995 Aug;4(8):1478-89. PMID:8520473<ref>PMID:8520473</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1agt" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Leiurus hebraeus]] | ||
| + | [[Category: Hidalgo P]] | ||
| + | [[Category: Kasibhatla C]] | ||
| + | [[Category: Krezel AM]] | ||
| + | [[Category: Mackinnon R]] | ||
| + | [[Category: Wagner G]] | ||
Current revision
SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY
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