2A9H

NMR structural studies of a potassium channel / charybdotoxin complex

2A9H の概要

• エントリーDOI: 10.2210/pdb2a9h/pdb
• NMR情報: BMRB: 6728
• 分子名称: Voltage-gated potassium channel, charybdotoxin (2 entities in total)
• 機能のキーワード: potassium channel, kcsa, membrane protein, metal transport
• 由来する生物種: Streptomyces lividans
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 71179.89

構造登録者

Yu, L.,Sun, C.,Song, D.,Shen, J.,Xu, N.,Gunasekera, A.,Hajduk, P.J.,Olejniczak, E.T. (登録日: 2005-07-11, 公開日: 2006-01-10, 最終更新日: 2024-11-20)

主引用文献

Yu, L.,Sun, C.,Song, D.,Shen, J.,Xu, N.,Gunasekera, A.,Hajduk, P.J.,Olejniczak, E.T.
Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.
Biochemistry, 44:15834-15841, 2005

PubMed Abstract: 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.

PubMed: 16313186
DOI: 10.1021/bi051656d

実験手法

SOLUTION NMR