1px9
From Proteopedia
(New page: 200px<br /><applet load="1px9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1px9" /> '''Solution structure of the native CnErg1 Ergt...) |
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'''Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel'''<br /> | '''Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The gamma-KTx-type scorpion toxins specific for K+ channels were found to | + | The gamma-KTx-type scorpion toxins specific for K+ channels were found to interact with ERG channels on the turret region, while alpha-KTx3.2 Agitoxin-2 binds to the pore region of the Shaker K+ channel, and alpha-KTx5.3 BmP05 binds to the intermediate region of the small-conductance calcium-activated K-channel (SK(Ca)). In order to explore the critical residues for gamma-KTx binding, we determined the NMR structure of native gamma-KTx1.1 (CnErg1), a 42 amino acid residues scorpion toxin isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann, and we used computational evolutionary trace (ET) analysis to predict possible structural and functional features of interacting surfaces. The 1H-NMR three-dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3J(NH-Halpha) and 10 hydrogen bonds. The structure is characterized by 2 segments of alpha-helices and a triple-stranded antiparallel beta-sheet stabilized by 4 disulfide bridges. The ET and structural analysis provided indication of the presence of two important amino acid residue clusters, one hydrophobic and the other hydrophilic, that should be involved in the surface contact between the toxin and the channel. Some features of the proposed interacting surface are discussed. |
==About this Structure== | ==About this Structure== | ||
| - | 1PX9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius]. Full crystallographic information is available from [http:// | + | 1PX9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PX9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Delepierre, M.]] | [[Category: Delepierre, M.]] | ||
[[Category: Frenal, K.]] | [[Category: Frenal, K.]] | ||
| - | [[Category: Gurrola, G | + | [[Category: Gurrola, G B.]] |
| - | [[Category: Possani, L | + | [[Category: Possani, L D.]] |
[[Category: Wecker, K.]] | [[Category: Wecker, K.]] | ||
[[Category: Wolff, N.]] | [[Category: Wolff, N.]] | ||
[[Category: alpha/beta molecular scaffold]] | [[Category: alpha/beta molecular scaffold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:27 2008'' |
Revision as of 12:33, 21 February 2008
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Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel
Overview
The gamma-KTx-type scorpion toxins specific for K+ channels were found to interact with ERG channels on the turret region, while alpha-KTx3.2 Agitoxin-2 binds to the pore region of the Shaker K+ channel, and alpha-KTx5.3 BmP05 binds to the intermediate region of the small-conductance calcium-activated K-channel (SK(Ca)). In order to explore the critical residues for gamma-KTx binding, we determined the NMR structure of native gamma-KTx1.1 (CnErg1), a 42 amino acid residues scorpion toxin isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann, and we used computational evolutionary trace (ET) analysis to predict possible structural and functional features of interacting surfaces. The 1H-NMR three-dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3J(NH-Halpha) and 10 hydrogen bonds. The structure is characterized by 2 segments of alpha-helices and a triple-stranded antiparallel beta-sheet stabilized by 4 disulfide bridges. The ET and structural analysis provided indication of the presence of two important amino acid residue clusters, one hydrophobic and the other hydrophilic, that should be involved in the surface contact between the toxin and the channel. Some features of the proposed interacting surface are discussed.
About this Structure
1PX9 is a Single protein structure of sequence from Centruroides noxius. Full crystallographic information is available from OCA.
Reference
Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels., Frenal K, Xu CQ, Wolff N, Wecker K, Gurrola GB, Zhu SY, Chi CW, Possani LD, Tytgat J, Delepierre M, Proteins. 2004 Aug 1;56(2):367-75. PMID:15211519
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