1agt

From Proteopedia

(Difference between revisions)

Current revision

SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY

Structural highlights

1agt 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, 17 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2]

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

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^[3]

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

References

↑ Takacs Z, Toups M, Kollewe A, Johnson E, Cuello LG, Driessens G, Biancalana M, Koide A, Ponte CG, Perozo E, Gajewski TF, Suarez-Kurtz G, Koide S, Goldstein SA. A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library. Proc Natl Acad Sci U S A. 2009 Dec 10. PMID:20007782
↑ Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, MacKinnon R. Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994 Jun 7;33(22):6834-9. PMID:8204618 doi:10.1021/bi00188a012
↑ Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G. Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. Protein Sci. 1995 Aug;4(8):1478-89. PMID:8520473

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY==
-<StructureSection load='1agt' size='340' side='right' caption='[[1agt]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''>
+<StructureSection load='1agt' size='340' side='right'caption='[[1agt]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1agt]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AGT FirstGlance]. <br>
+<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1agt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1agt OCA], [http://pdbe.org/1agt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1agt RCSB], [http://www.ebi.ac.uk/pdbsum/1agt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1agt ProSAT]</span></td></tr>
+</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 ==
-[[http://www.uniprot.org/uniprot/KAX32_LEIQH KAX32_LEIQH]] Potent inhibitor of shaker potassium channels as well as the mammalian homologs of shaker.
+[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>
+    <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/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 29: / Line 30: @@
 ==See Also==
-*[[Potassium channel toxin|Potassium channel toxin]]
+*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Hidalgo, P]]
+[[Category: Large Structures]]
-[[Category: Kasibhatla, C]]
+[[Category: Leiurus hebraeus]]
-[[Category: Krezel, A M]]
+[[Category: Hidalgo P]]
-[[Category: Mackinnon, R]]
+[[Category: Kasibhatla C]]
-[[Category: Wagner, G]]
+[[Category: Krezel AM]]
-[[Category: Neurotoxin]]
+[[Category: Mackinnon R]]
-[[Category: Potassium channel blocker]]
+[[Category: Wagner G]]

1agt

From Proteopedia

Current revision

SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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