2a9h

NMR structural studies of a potassium channel / charybdotoxin complex

spinqualitylabelsall models 2a9h, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a9h is a 5 chain structure with sequence from Streptomyces lividans. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: PCA Gene: kcsA, skc1 (Streptomyces lividans) Resources: FirstGlance, OCA, RCSB, PDBsum Function [KCSA_STRLI] Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium Channel

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