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• W2071738649 abstract "To further investigate the effect of single amino acid substitution on the structure and function of the gramicidin channel, an analogue of gramicidin A (GA) has been synthesized in which Trp15 is replaced by Gly in the critical aqueous interface and cation binding region. The structure of Gly15-GA incorporated into SDS micelles has been determined using a combination of 2D-NMR spectroscopy and molecular modeling. Like the parent GA, Gly15-GA forms a dimeric channel composed of two single-stranded, right-handed β6.3-helices joined by hydrogen bonds between their N-termini. The replacement of Trp15 by Gly does not have a significant effect on backbone structure or side chain conformations with the exception of Trp11 in which the indole ring is rotated away from the channel axis. Measurement of the equilibrium binding constants and ΔG for the binding of monovalent cations to GA and Gly15-GA channels incorporated into PC vesicles using 205Tl NMR spectroscopy shows that monovalent cations bind much more weakly to the Gly15-GA channel entrance than to GA channels. Utilizing the magnetization inversion transfer NMR technique, the transport of Na+ ions through GA and Gly15-GA channels incorporated into PC/PG vesicles has been investigated. The Gly15 substitution produces an increase in the activation enthalpy of transport and thus a significant decrease in the transport rate of the Na+ ion is observed. The single-channel appearances show that the conducting channels have a single, well-defined structure. Consistent with the NMR results, the single-channel conductances are reduced by 30% and the lifetimes by 70%. It is concluded that the decrease in cation binding, transport, and conductance in Gly15-GA results from the removal of the Trp15 dipole and, to a lesser extent, the change in orientation of Trp11." @default.
• W2071738649 created "2016-06-24" @default.
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• W2071738649 date "2003-01-23" @default.
• W2071738649 modified "2023-09-25" @default.
• W2071738649 title "The Structure, Cation Binding, Transport, and Conductance of Gly₁₅-Gramicidin A Incorporated into SDS Micelles and PC/PG Vesicles^," @default.
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• W2071738649 doi "https://doi.org/10.1021/bi0204286" @default.
• W2071738649 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12578352" @default.
• W2071738649 hasPublicationYear "2003" @default.
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