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Cover Picture: Conformational Flexibility in the Binding Surface of the Potassium Channel Blocker ShK (ChemBioChem 16/2014)
Author(s) -
Sher Inbal,
Chang Shih Chieh,
Li Ying,
Chhabra Sandeep,
Palmer Arthur G.,
Norton Raymond S.,
Chill Jordan H.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201490055
Subject(s) - conformational isomerism , chemistry , potassium channel blocker , molecular dynamics , potassium channel , stereochemistry , helix (gastropod) , crystallography , biophysics , potassium , computational chemistry , molecule , organic chemistry , biology , ecology , snail
The cover picture shows NMR detecting previously unobserved backbone motions of the 35‐residue marine potassium channel blocker ShK. By measuring the relaxation of 15 N 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 p. 2402 ff. , 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.