Cover Picture: Conformational Flexibility in the Binding Surface of the Potassium Channel Blocker ShK (ChemBioChem 16/2014). Issue 16 (3rd November 2014)

• Record Type: Journal Article
• Authors: Sher, Inbal; Chang, Shih Chieh; Li, Ying; Chhabra, Sandeep; Palmer, Arthur G.; Norton, Raymond S.; Chill, Jordan H.
• Is Part Of: Chembiochem. Volume 15:Issue 16(2014)
• Page Start: 2317
• Page End: 2317
• Publication Date: 2014-11-03
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201490055
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>The cover picture shows</bold> NMR detecting previously unobserved backbone motions of the 35‐residue marine potassium channel blocker ShK. By measuring the relaxation of ¹⁵N magnetic moments of ShK (PDB ID: 1roo, shown as a white surface) under different experimental conditions, the existence of a lowly populated conformer was inferred. As described in the article by J. H. Chill et al. on <ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">p. 2402 ff.</ext-link>, relaxation dispersion curves (below, left) identified amino acids influenced by this "molecular melodrama", thus focusing our attention on the helix–kink–helix motif (red) and, in particular, on residues Lys22 and Tyr23 (blue and magenta, respectively). Increased exposure of Tyr23 in the minor conformer is apparently a key molecular event in ShK blocking of voltage‐gated potassium channels (top right); this underscores the potential role of conformation selection in the binding of polypeptidic inhibitors to their biological targets.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgh2chdkzg5" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>