2axk
From Proteopedia
(New page: 200px<br /><applet load="2axk" size="450" color="white" frame="true" align="right" spinBox="true" caption="2axk" /> '''Solution structure of discrepin, a scorpion ...) |
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| - | [[Image:2axk.gif|left|200px]]<br /><applet load="2axk" size=" | + | [[Image:2axk.gif|left|200px]]<br /><applet load="2axk" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.'''<br /> | '''Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Discrepin, isolated from the venom of the Venezuelan scorpion Tityus | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2AXK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 2AXK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Corzo, G.]] | [[Category: Corzo, G.]] | ||
[[Category: Delepierre, M.]] | [[Category: Delepierre, M.]] | ||
| - | [[Category: Martin-Eauclaire, M | + | [[Category: Martin-Eauclaire, M F.]] |
| - | [[Category: Murgia, A | + | [[Category: Murgia, A R.]] |
| - | [[Category: Possani, L | + | [[Category: Possani, L D.]] |
[[Category: Prestipino, G.]] | [[Category: Prestipino, G.]] | ||
[[Category: Prochnicka-Chalufour, A.]] | [[Category: Prochnicka-Chalufour, A.]] | ||
[[Category: Satake, H.]] | [[Category: Satake, H.]] | ||
| - | [[Category: Suze, G | + | [[Category: Suze, G D.]] |
[[Category: a-current]] | [[Category: a-current]] | ||
[[Category: discrepin]] | [[Category: discrepin]] | ||
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[[Category: scorpion toxin]] | [[Category: scorpion toxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:10 2008'' |
Revision as of 14:32, 21 February 2008
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Solution structure of discrepin, a scorpion venom toxin blocking K+ channels.
Overview
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.
About this Structure
2AXK is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
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
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