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2axk
From Proteopedia
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| - | [[Image:2axk.gif|left|200px]]<br /><applet load="2axk" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2axk" /> | ||
| - | '''Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.'''<br /> | ||
| - | == | + | ==Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.== |
| + | <StructureSection load='2axk' size='340' side='right'caption='[[2axk]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2axk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tityus_discrepans Tityus discrepans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AXK FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2axk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2axk OCA], [https://pdbe.org/2axk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2axk RCSB], [https://www.ebi.ac.uk/pdbsum/2axk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2axk ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KA156_TITDI KA156_TITDI] Irreversibly blocks the A-type voltage-gated potassium channels in rat cerebellum granular cells.<ref>PMID:15369825</ref> <ref>PMID:16460026</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Discrepin, isolated from the venom of the Venezuelan scorpion Tityus discrepans, blocks preferentially the I(A) currents of the voltage-dependent K+ channel of rat cerebellum granular cells in an irreversible way. It contains 38 amino acid residues with a pyroglutamic acid as the N-terminal residue [D'Suze, G., Batista, C. V., Frau, A., Murgia, A. R., Zamudio, F. Z., Sevcik, C., Possani, L. D., and Prestipino, G. (2004) Arch. Biochem. Biophys. 430, 256-63]. It is the most distinctive member of the alpha-KTx15 subfamily of scorpion toxins. Six members of the alpha-KTx15 subfamily have been reported so far to be specific for this subtype of the K+ channel; however, none of them have had their three-dimensional structure determined, and no information for the residues possibly involved in channel recognition and binding is available. Natural discrepin (n-discrepin) was prepared from scorpion venom, and its synthetic analogue (s-discrepin) was obtained by solid-phase synthesis. Analysis of two-dimensional 1H NMR spectra of n- and s-discrepin indicates that both peptides have the same structure. Here we report the solution structure of s-discrepin determined by NMR using 565 meaningful distance constraints derived from the volume integration of the two-dimensional NOESY spectrum, 22 dihedrals, and three hydrogen bonds. Discrepin displays the alpha/beta scaffold, characteristic of scorpion toxins. Some features of the proposed interacting surface between the toxin and channel as well as the opposite "alpha-helix surface" are discussed in comparison with those of other alpha-KTx15 members. Both n- and s-discrepin exhibit similar physiological actions as verified by patch-clamp and binding and displacement experiments. | Discrepin, isolated from the venom of the Venezuelan scorpion Tityus discrepans, blocks preferentially the I(A) currents of the voltage-dependent K+ channel of rat cerebellum granular cells in an irreversible way. It contains 38 amino acid residues with a pyroglutamic acid as the N-terminal residue [D'Suze, G., Batista, C. V., Frau, A., Murgia, A. R., Zamudio, F. Z., Sevcik, C., Possani, L. D., and Prestipino, G. (2004) Arch. Biochem. Biophys. 430, 256-63]. It is the most distinctive member of the alpha-KTx15 subfamily of scorpion toxins. Six members of the alpha-KTx15 subfamily have been reported so far to be specific for this subtype of the K+ channel; however, none of them have had their three-dimensional structure determined, and no information for the residues possibly involved in channel recognition and binding is available. Natural discrepin (n-discrepin) was prepared from scorpion venom, and its synthetic analogue (s-discrepin) was obtained by solid-phase synthesis. Analysis of two-dimensional 1H NMR spectra of n- and s-discrepin indicates that both peptides have the same structure. Here we report the solution structure of s-discrepin determined by NMR using 565 meaningful distance constraints derived from the volume integration of the two-dimensional NOESY spectrum, 22 dihedrals, and three hydrogen bonds. Discrepin displays the alpha/beta scaffold, characteristic of scorpion toxins. Some features of the proposed interacting surface between the toxin and channel as well as the opposite "alpha-helix surface" are discussed in comparison with those of other alpha-KTx15 members. Both n- and s-discrepin exhibit similar physiological actions as verified by patch-clamp and binding and displacement experiments. | ||
| - | + | Solution structure of discrepin, a new K+-channel blocking peptide from the alpha-KTx15 subfamily.,Prochnicka-Chalufour A, Corzo G, Satake H, Martin-Eauclaire MF, Murgia AR, Prestipino G, D'Suze G, Possani LD, Delepierre M Biochemistry. 2006 Feb 14;45(6):1795-804. PMID:16460026<ref>PMID:16460026</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2axk" 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: Tityus discrepans]] | ||
| + | [[Category: Corzo G]] | ||
| + | [[Category: D'Suze G]] | ||
| + | [[Category: Delepierre M]] | ||
| + | [[Category: Martin-Eauclaire M-F]] | ||
| + | [[Category: Murgia AR]] | ||
| + | [[Category: Possani LD]] | ||
| + | [[Category: Prestipino G]] | ||
| + | [[Category: Prochnicka-Chalufour A]] | ||
| + | [[Category: Satake H]] | ||
Current revision
Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.
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