Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles

Gramicidins A, B, and C are the three most abundant, naturally occurring an alogues of this family of channel-forming antibiotic. GB and GC differ from the parent pentadecapeptide, GA, by single residue mutations, W11F and W11 Y, respectively. Although these mutations occur in the cation binding regio n of the channel, they do not affect monovalent cation specificity, but are known to alter cation-binding affinities, thermodynamic parameters of cati on binding, conductance and the activation energy for ion transport. The st ructures of all three analogues incorporated into deuterated sodium dodecyl sulfate micelles have been obtained using solution state 2D-NMR spectrosco py and molecular modeling. For the first time, a rigorous comparison of the 3D structures of these analogues reveals that the amino acid substitutions do not have a significant effect on backbone conformation, thus eliminatin g channel differences as the cause of variations in transport properties. V ariable positions of methyl groups in valine and leucine residues 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 orient ation of the dipole moment at residue I I are responsible for altering mono valent cation transport.