A solution NMR study of the selectively 13C, 15N-labeled peptaibol chrysospermin C in methanol

Abstract: The conformation of the 19-residue peptaibol chrysospermin C in methanol has been investigated by NMR spectroscopy using selective ¹⁵N and ¹³C labeling of the α-aminoisobutyric acid (Aib) residues. Complete ¹H and ¹³C sequential assignments, including stereospecific assignments for the heavily overlapped resonances from the two C^β methyl groups of the eight Aib residues, are reported for a peptaibol for the first time. An Aib residue followed by a Pro is an exception to previous suggestions regarding stereospecific assignment of the two C^β methyl groups of Aib residues. Local nuclear Overhauser effects and ³J_HNC and ³J_HNCβ scalar couplings indicate that the φ angles of the Aib residues are restricted sterically to local conformations consistent with right-handed helices. Despite these constraints on the eight Aib residues, the NMR data for chrysospermin C in methanol are generally most consistent with an ensemble of transient conformations, including backbone conformations inconsistent with helical structures. Initial NMR measurements for chrysospermin C bound to micelles suggest structural and dynamic differences relative to alamethicin bound to micelles which may be related to differences in gating voltages for formation of ion channels.