2a9h
From Proteopedia
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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
Page seeded by OCA on Wed Nov 21 08:00:08 2007
Categories: Single protein | Streptomyces lividans | Gunasekera, A. | Hajduk, P.J. | Olejniczak, E.T. | Shen, J. | Song, D. | Sun, C. | Xu, N. | Yu, L. | Kcsa | Membrane protein | Nmr | Potassium channel | Structure
