2a9h

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(New page: 200px<br /><applet load="2a9h" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a9h" /> '''NMR structural studies of a potassium channe...)
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'''NMR structural studies of a potassium channel / charybdotoxin complex'''<br />
'''NMR structural studies of a potassium channel / charybdotoxin complex'''<br />
==Overview==
==Overview==
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Ion channels play critical roles in signaling processes and are attractive, targets for treating various diseases. Here we describe an NMR-based, strategy for structural analyses of potassium channel-ligand complexes, using KcsA (residues 1-132, with six mutations to impart toxin binding and, to mimic the eukaryotic hERG channel). Using this approach, we determined, the solution structure of KcsA in complex with the high-affinity peptide, antagonist charybdotoxin. The structural data reveal how charybdotoxin, binds to the closed form of KcsA and makes specific contacts with the, extracellular surface of the ion channel, resulting in pore blockage. This, represents the first direct structural information about an ion channel, complexed to a peptide antagonist and provides an experimental framework, for understanding and interpreting earlier mutational analyses. The, strategy presented here overcomes many of the limitations of conventional, NMR approaches to helical membrane protein structure determination and can, be applied in the study of the binding of druglike molecules to this, important class of proteins.
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Ion channels play critical roles in signaling processes and are attractive targets for treating various diseases. Here we describe an NMR-based strategy for structural analyses of potassium channel-ligand complexes using KcsA (residues 1-132, with six mutations to impart toxin binding and to mimic the eukaryotic hERG channel). Using this approach, we determined the solution structure of KcsA in complex with the high-affinity peptide antagonist charybdotoxin. The structural data reveal how charybdotoxin binds to the closed form of KcsA and makes specific contacts with the extracellular surface of the ion channel, resulting in pore blockage. This represents the first direct structural information about an ion channel complexed to a peptide antagonist and provides an experimental framework for understanding and interpreting earlier mutational analyses. The strategy presented here overcomes many of the limitations of conventional NMR approaches to helical membrane protein structure determination and can be applied in the study of the binding of druglike molecules to this important class of proteins.
==About this Structure==
==About this Structure==
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2A9H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A9H OCA].
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2A9H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A9H OCA].
==Reference==
==Reference==
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[[Category: Streptomyces lividans]]
[[Category: Streptomyces lividans]]
[[Category: Gunasekera, A.]]
[[Category: Gunasekera, A.]]
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[[Category: Hajduk, P.J.]]
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[[Category: Hajduk, P J.]]
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[[Category: Olejniczak, E.T.]]
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[[Category: Olejniczak, E T.]]
[[Category: Shen, J.]]
[[Category: Shen, J.]]
[[Category: Song, D.]]
[[Category: Song, D.]]
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[[Category: structure]]
[[Category: structure]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:00:08 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:11 2008''

Revision as of 14:25, 21 February 2008

Image:2a9h.gif

2a9h

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NMR structural studies of a potassium channel / charybdotoxin complex

Overview

Ion channels play critical roles in signaling processes and are attractive targets for treating various diseases. Here we describe an NMR-based strategy for structural analyses of potassium channel-ligand complexes using KcsA (residues 1-132, with six mutations to impart toxin binding and to mimic the eukaryotic hERG channel). Using this approach, we determined the solution structure of KcsA in complex with the high-affinity peptide antagonist charybdotoxin. The structural data reveal how charybdotoxin binds to the closed form of KcsA and makes specific contacts with the extracellular surface of the ion channel, resulting in pore blockage. This represents the first direct structural information about an ion channel complexed to a peptide antagonist and provides an experimental framework for understanding and interpreting earlier mutational analyses. The strategy presented here overcomes many of the limitations of conventional NMR approaches to helical membrane protein structure determination and can be applied in the study of the binding of druglike molecules to this important class of proteins.

About this Structure

2A9H is a Single protein structure of sequence from Streptomyces lividans. Full crystallographic information is available from OCA.

Reference

Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex., Yu L, Sun C, Song D, Shen J, Xu N, Gunasekera A, Hajduk PJ, Olejniczak ET, Biochemistry. 2005 Dec 6;44(48):15834-41. PMID:16313186

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