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1agt

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(New page: 200px<br /><applet load="1agt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1agt" /> '''SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL ...)
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'''SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY'''<br />
'''SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY'''<br />
==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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1AGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AGT OCA].
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1AGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGT OCA].
==Reference==
==Reference==
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[[Category: Hidalgo, P.]]
[[Category: Hidalgo, P.]]
[[Category: Kasibhatla, C.]]
[[Category: Kasibhatla, C.]]
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[[Category: Krezel, A.M.]]
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[[Category: Krezel, A M.]]
[[Category: Mackinnon, R.]]
[[Category: Mackinnon, R.]]
[[Category: Wagner, G.]]
[[Category: Wagner, G.]]
[[Category: potassium channel blocker]]
[[Category: potassium channel blocker]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:50:21 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:44:20 2008''

Revision as of 09:44, 21 February 2008


1agt

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

Overview

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.

About this Structure

1AGT is a Single protein structure of sequence from Leiurus quinquestriatus hebraeus. Full crystallographic information is available from OCA.

Reference

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

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