| Abstract
| - Gramicidins A, B, and C are the three most abundant, naturally occurring analogues of thisfamily of channel-forming antibiotic. GB and GC differ from the parent pentadecapeptide, GA, by singleresidue mutations, W11F and W11Y, respectively. Although these mutations occur in the cation bindingregion of the channel, they do not affect monovalent cation specificity, but are known to alter cation-binding affinities, thermodynamic parameters of cation binding, conductance and the activation energyfor ion transport. The structures of all three analogues incorporated into deuterated sodium dodecyl sulfatemicelles have been obtained using solution state 2D-NMR spectroscopy and molecular modeling. For thefirst time, a rigorous comparison of the 3D structures of these analogues reveals that the amino acidsubstitutions do not have a significant effect on backbone conformation, thus eliminating channel differencesas the cause of variations in transport properties. Variable positions of methyl groups in valine and leucineresidues have been linked to molecular motions and are not likely to affect ion flow through the channel.Thus, it is concluded that changes in the magnitude and orientation of the dipole moment at residue 11are responsible for altering monovalent cation transport.
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